Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility

Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Natalie E. King [verfasserIn] Jo-Maree Courtney [verfasserIn] Lachlan S. Brown [verfasserIn] Alastair J. Fortune [verfasserIn] Nicholas B. Blackburn [verfasserIn] Jessica L. Fletcher [verfasserIn] Jake M. Cashion [verfasserIn] Jana Talbot [verfasserIn] Alice Pébay [verfasserIn] Alex W. Hewitt [verfasserIn] Gary P. Morris [verfasserIn] Kaylene M. Young [verfasserIn] Anthony L. Cook [verfasserIn] Brad A. Sutherland [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	Induced pluripotent stem cells (iPSCs) Pericytes Human brain vascular pericytes (HBVPs) Proliferation Platelet-derived growth factor BB (PDGF-BB) Platelet-derived growth factor receptor β (PDGFRβ)

Übergeordnetes Werk:	In: Stem Cell Research & Therapy - BMC, 2015, 15(2024), 1, Seite 19
Übergeordnetes Werk:	volume:15 ; year:2024 ; number:1 ; pages:19

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13287-024-03671-x

Katalog-ID:	DOAJ092177964

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245	1	0	\|a Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility
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520			\|a Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases.
650		4	\|a Induced pluripotent stem cells (iPSCs)
650		4	\|a Pericytes
650		4	\|a Human brain vascular pericytes (HBVPs)
650		4	\|a Proliferation
650		4	\|a Platelet-derived growth factor BB (PDGF-BB)
650		4	\|a Platelet-derived growth factor receptor β (PDGFRβ)
653		0	\|a Medicine (General)
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700	0		\|a Jo-Maree Courtney \|e verfasserin \|4 aut
700	0		\|a Lachlan S. Brown \|e verfasserin \|4 aut
700	0		\|a Alastair J. Fortune \|e verfasserin \|4 aut
700	0		\|a Nicholas B. Blackburn \|e verfasserin \|4 aut
700	0		\|a Jessica L. Fletcher \|e verfasserin \|4 aut
700	0		\|a Jake M. Cashion \|e verfasserin \|4 aut
700	0		\|a Jana Talbot \|e verfasserin \|4 aut
700	0		\|a Alice Pébay \|e verfasserin \|4 aut
700	0		\|a Alex W. Hewitt \|e verfasserin \|4 aut
700	0		\|a Gary P. Morris \|e verfasserin \|4 aut
700	0		\|a Kaylene M. Young \|e verfasserin \|4 aut
700	0		\|a Anthony L. Cook \|e verfasserin \|4 aut
700	0		\|a Brad A. Sutherland \|e verfasserin \|4 aut
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allfields	10.1186/s13287-024-03671-x doi (DE-627)DOAJ092177964 (DE-599)DOAJc8c8c85bb5db476ea1a3b1f8afc26262 DE-627 ger DE-627 rakwb eng R5-920 QD415-436 Natalie E. King verfasserin aut Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases. Induced pluripotent stem cells (iPSCs) Pericytes Human brain vascular pericytes (HBVPs) Proliferation Platelet-derived growth factor BB (PDGF-BB) Platelet-derived growth factor receptor β (PDGFRβ) Medicine (General) Biochemistry Jo-Maree Courtney verfasserin aut Lachlan S. Brown verfasserin aut Alastair J. Fortune verfasserin aut Nicholas B. Blackburn verfasserin aut Jessica L. Fletcher verfasserin aut Jake M. Cashion verfasserin aut Jana Talbot verfasserin aut Alice Pébay verfasserin aut Alex W. Hewitt verfasserin aut Gary P. Morris verfasserin aut Kaylene M. Young verfasserin aut Anthony L. Cook verfasserin aut Brad A. Sutherland verfasserin aut In Stem Cell Research & Therapy BMC, 2015 15(2024), 1, Seite 19 (DE-627)624251047 (DE-600)2548671-8 17576512 nnns volume:15 year:2024 number:1 pages:19 https://doi.org/10.1186/s13287-024-03671-x kostenfrei https://doaj.org/article/c8c8c85bb5db476ea1a3b1f8afc26262 kostenfrei https://doi.org/10.1186/s13287-024-03671-x kostenfrei https://doaj.org/toc/1757-6512 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2024 1 19
spelling	10.1186/s13287-024-03671-x doi (DE-627)DOAJ092177964 (DE-599)DOAJc8c8c85bb5db476ea1a3b1f8afc26262 DE-627 ger DE-627 rakwb eng R5-920 QD415-436 Natalie E. King verfasserin aut Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases. Induced pluripotent stem cells (iPSCs) Pericytes Human brain vascular pericytes (HBVPs) Proliferation Platelet-derived growth factor BB (PDGF-BB) Platelet-derived growth factor receptor β (PDGFRβ) Medicine (General) Biochemistry Jo-Maree Courtney verfasserin aut Lachlan S. Brown verfasserin aut Alastair J. Fortune verfasserin aut Nicholas B. Blackburn verfasserin aut Jessica L. Fletcher verfasserin aut Jake M. Cashion verfasserin aut Jana Talbot verfasserin aut Alice Pébay verfasserin aut Alex W. Hewitt verfasserin aut Gary P. Morris verfasserin aut Kaylene M. Young verfasserin aut Anthony L. Cook verfasserin aut Brad A. Sutherland verfasserin aut In Stem Cell Research & Therapy BMC, 2015 15(2024), 1, Seite 19 (DE-627)624251047 (DE-600)2548671-8 17576512 nnns volume:15 year:2024 number:1 pages:19 https://doi.org/10.1186/s13287-024-03671-x kostenfrei https://doaj.org/article/c8c8c85bb5db476ea1a3b1f8afc26262 kostenfrei https://doi.org/10.1186/s13287-024-03671-x kostenfrei https://doaj.org/toc/1757-6512 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2024 1 19
allfields_unstemmed	10.1186/s13287-024-03671-x doi (DE-627)DOAJ092177964 (DE-599)DOAJc8c8c85bb5db476ea1a3b1f8afc26262 DE-627 ger DE-627 rakwb eng R5-920 QD415-436 Natalie E. King verfasserin aut Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases. Induced pluripotent stem cells (iPSCs) Pericytes Human brain vascular pericytes (HBVPs) Proliferation Platelet-derived growth factor BB (PDGF-BB) Platelet-derived growth factor receptor β (PDGFRβ) Medicine (General) Biochemistry Jo-Maree Courtney verfasserin aut Lachlan S. Brown verfasserin aut Alastair J. Fortune verfasserin aut Nicholas B. Blackburn verfasserin aut Jessica L. Fletcher verfasserin aut Jake M. Cashion verfasserin aut Jana Talbot verfasserin aut Alice Pébay verfasserin aut Alex W. Hewitt verfasserin aut Gary P. Morris verfasserin aut Kaylene M. Young verfasserin aut Anthony L. Cook verfasserin aut Brad A. Sutherland verfasserin aut In Stem Cell Research & Therapy BMC, 2015 15(2024), 1, Seite 19 (DE-627)624251047 (DE-600)2548671-8 17576512 nnns volume:15 year:2024 number:1 pages:19 https://doi.org/10.1186/s13287-024-03671-x kostenfrei https://doaj.org/article/c8c8c85bb5db476ea1a3b1f8afc26262 kostenfrei https://doi.org/10.1186/s13287-024-03671-x kostenfrei https://doaj.org/toc/1757-6512 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2024 1 19
allfieldsGer	10.1186/s13287-024-03671-x doi (DE-627)DOAJ092177964 (DE-599)DOAJc8c8c85bb5db476ea1a3b1f8afc26262 DE-627 ger DE-627 rakwb eng R5-920 QD415-436 Natalie E. King verfasserin aut Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases. Induced pluripotent stem cells (iPSCs) Pericytes Human brain vascular pericytes (HBVPs) Proliferation Platelet-derived growth factor BB (PDGF-BB) Platelet-derived growth factor receptor β (PDGFRβ) Medicine (General) Biochemistry Jo-Maree Courtney verfasserin aut Lachlan S. Brown verfasserin aut Alastair J. Fortune verfasserin aut Nicholas B. Blackburn verfasserin aut Jessica L. Fletcher verfasserin aut Jake M. Cashion verfasserin aut Jana Talbot verfasserin aut Alice Pébay verfasserin aut Alex W. Hewitt verfasserin aut Gary P. Morris verfasserin aut Kaylene M. Young verfasserin aut Anthony L. Cook verfasserin aut Brad A. Sutherland verfasserin aut In Stem Cell Research & Therapy BMC, 2015 15(2024), 1, Seite 19 (DE-627)624251047 (DE-600)2548671-8 17576512 nnns volume:15 year:2024 number:1 pages:19 https://doi.org/10.1186/s13287-024-03671-x kostenfrei https://doaj.org/article/c8c8c85bb5db476ea1a3b1f8afc26262 kostenfrei https://doi.org/10.1186/s13287-024-03671-x kostenfrei https://doaj.org/toc/1757-6512 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2024 1 19
allfieldsSound	10.1186/s13287-024-03671-x doi (DE-627)DOAJ092177964 (DE-599)DOAJc8c8c85bb5db476ea1a3b1f8afc26262 DE-627 ger DE-627 rakwb eng R5-920 QD415-436 Natalie E. King verfasserin aut Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases. Induced pluripotent stem cells (iPSCs) Pericytes Human brain vascular pericytes (HBVPs) Proliferation Platelet-derived growth factor BB (PDGF-BB) Platelet-derived growth factor receptor β (PDGFRβ) Medicine (General) Biochemistry Jo-Maree Courtney verfasserin aut Lachlan S. Brown verfasserin aut Alastair J. Fortune verfasserin aut Nicholas B. Blackburn verfasserin aut Jessica L. Fletcher verfasserin aut Jake M. Cashion verfasserin aut Jana Talbot verfasserin aut Alice Pébay verfasserin aut Alex W. Hewitt verfasserin aut Gary P. Morris verfasserin aut Kaylene M. Young verfasserin aut Anthony L. Cook verfasserin aut Brad A. Sutherland verfasserin aut In Stem Cell Research & Therapy BMC, 2015 15(2024), 1, Seite 19 (DE-627)624251047 (DE-600)2548671-8 17576512 nnns volume:15 year:2024 number:1 pages:19 https://doi.org/10.1186/s13287-024-03671-x kostenfrei https://doaj.org/article/c8c8c85bb5db476ea1a3b1f8afc26262 kostenfrei https://doi.org/10.1186/s13287-024-03671-x kostenfrei https://doaj.org/toc/1757-6512 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2024 1 19
language	English
source	In Stem Cell Research & Therapy 15(2024), 1, Seite 19 volume:15 year:2024 number:1 pages:19
sourceStr	In Stem Cell Research & Therapy 15(2024), 1, Seite 19 volume:15 year:2024 number:1 pages:19
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Induced pluripotent stem cells (iPSCs) Pericytes Human brain vascular pericytes (HBVPs) Proliferation Platelet-derived growth factor BB (PDGF-BB) Platelet-derived growth factor receptor β (PDGFRβ) Medicine (General) Biochemistry
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container_title	Stem Cell Research & Therapy
authorswithroles_txt_mv	Natalie E. King @@aut@@ Jo-Maree Courtney @@aut@@ Lachlan S. Brown @@aut@@ Alastair J. Fortune @@aut@@ Nicholas B. Blackburn @@aut@@ Jessica L. Fletcher @@aut@@ Jake M. Cashion @@aut@@ Jana Talbot @@aut@@ Alice Pébay @@aut@@ Alex W. Hewitt @@aut@@ Gary P. Morris @@aut@@ Kaylene M. Young @@aut@@ Anthony L. Cook @@aut@@ Brad A. Sutherland @@aut@@
publishDateDaySort_date	2024-01-01T00:00:00Z
hierarchy_top_id	624251047
id	DOAJ092177964
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ092177964</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414093818.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240412s2024 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13287-024-03671-x</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ092177964</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJc8c8c85bb5db476ea1a3b1f8afc26262</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">R5-920</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QD415-436</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Natalie E. King</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Induced pluripotent stem cells (iPSCs)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pericytes</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Human brain vascular pericytes (HBVPs)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Proliferation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Platelet-derived growth factor BB (PDGF-BB)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Platelet-derived growth factor receptor β (PDGFRβ)</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine (General)</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biochemistry</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jo-Maree Courtney</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lachlan S. Brown</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alastair J. Fortune</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nicholas B. Blackburn</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jessica L. Fletcher</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jake M. 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callnumber-first	R - Medicine
author	Natalie E. King
spellingShingle	Natalie E. King misc R5-920 misc QD415-436 misc Induced pluripotent stem cells (iPSCs) misc Pericytes misc Human brain vascular pericytes (HBVPs) misc Proliferation misc Platelet-derived growth factor BB (PDGF-BB) misc Platelet-derived growth factor receptor β (PDGFRβ) misc Medicine (General) misc Biochemistry Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility
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topic_title	R5-920 QD415-436 Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility Induced pluripotent stem cells (iPSCs) Pericytes Human brain vascular pericytes (HBVPs) Proliferation Platelet-derived growth factor BB (PDGF-BB) Platelet-derived growth factor receptor β (PDGFRβ)
topic	misc R5-920 misc QD415-436 misc Induced pluripotent stem cells (iPSCs) misc Pericytes misc Human brain vascular pericytes (HBVPs) misc Proliferation misc Platelet-derived growth factor BB (PDGF-BB) misc Platelet-derived growth factor receptor β (PDGFRβ) misc Medicine (General) misc Biochemistry
topic_unstemmed	misc R5-920 misc QD415-436 misc Induced pluripotent stem cells (iPSCs) misc Pericytes misc Human brain vascular pericytes (HBVPs) misc Proliferation misc Platelet-derived growth factor BB (PDGF-BB) misc Platelet-derived growth factor receptor β (PDGFRβ) misc Medicine (General) misc Biochemistry
topic_browse	misc R5-920 misc QD415-436 misc Induced pluripotent stem cells (iPSCs) misc Pericytes misc Human brain vascular pericytes (HBVPs) misc Proliferation misc Platelet-derived growth factor BB (PDGF-BB) misc Platelet-derived growth factor receptor β (PDGFRβ) misc Medicine (General) misc Biochemistry
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title	Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility
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title_full	Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility
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author_browse	Natalie E. King Jo-Maree Courtney Lachlan S. Brown Alastair J. Fortune Nicholas B. Blackburn Jessica L. Fletcher Jake M. Cashion Jana Talbot Alice Pébay Alex W. Hewitt Gary P. Morris Kaylene M. Young Anthony L. Cook Brad A. Sutherland
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title_sort	induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility
callnumber	R5-920
title_auth	Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility
abstract	Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases.
abstractGer	Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases.
abstract_unstemmed	Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases.
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title_short	Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility
url	https://doi.org/10.1186/s13287-024-03671-x https://doaj.org/article/c8c8c85bb5db476ea1a3b1f8afc26262 https://doaj.org/toc/1757-6512
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author2Str	Jo-Maree Courtney Lachlan S. Brown Alastair J. Fortune Nicholas B. Blackburn Jessica L. Fletcher Jake M. Cashion Jana Talbot Alice Pébay Alex W. Hewitt Gary P. Morris Kaylene M. Young Anthony L. Cook Brad A. Sutherland
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To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. 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Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility

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