Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis

Diffuse grade II IDH-mutant gliomas are slow-growing brain tumors that progress into high-grade gliomas. They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell dive...
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Autor*in:	Meera Augustus [verfasserIn] Donovan Pineau [verfasserIn] Franck Aimond [verfasserIn] Safa Azar [verfasserIn] Davide Lecca [verfasserIn] Frédérique Scamps [verfasserIn] Sophie Muxel [verfasserIn] Amélie Darlix [verfasserIn] William Ritchie [verfasserIn] Catherine Gozé [verfasserIn] Valérie Rigau [verfasserIn] Hugues Duffau [verfasserIn] Jean-Philippe Hugnot [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	brain tumors diffuse grade II IDH-mutant glioma diffuse IDH1-mutant gliomas cellular heterogeneity NOTCH1 pathway BMP

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 13(2021), 9, p 2107
Übergeordnetes Werk:	volume:13 ; year:2021 ; number:9, p 2107

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers13092107

Katalog-ID:	DOAJ001835467

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520			\|a Diffuse grade II IDH-mutant gliomas are slow-growing brain tumors that progress into high-grade gliomas. They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell diversity is also ill-defined. Here, we report that SOX9 and OLIG1 transcription factors, which specifically label astrocytes and oligodendrocytes in the normal brain, revealed the presence of two largely nonoverlapping tumoral populations in IDH1-mutant oligodendrogliomas and astrocytomas. Astrocyte-like SOX9<sup<+</sup< cells additionally stained for APOE, CRYAB, ID4, KCNN3, while oligodendrocyte-like OLIG1<sup<+</sup< cells stained for ASCL1, EGFR, IDH1, PDGFRA, PTPRZ1, SOX4, and SOX8. GPR17, an oligodendrocytic marker, was expressed by both cells. These two subpopulations appear to have distinct BMP, NOTCH1, and MAPK active pathways as stainings for BMP4, HEY1, HEY2, p-SMAD1/5 and p-ERK were higher in SOX9<sup<+</sup< cells. We used primary cultures and a new cell line to explore the influence of NOTCH1 activation and BMP treatment on the IDH1-mutant glioma cell phenotype. This revealed that NOTCH1 globally reduced oligodendrocytic markers and IDH1 expression while upregulating <i<APOE, CRYAB, HEY1/2,</i< and an electrophysiologically-active Ca<sup<2+</sup<-activated apamin-sensitive K<sup<+</sup< channel (KCNN3/SK3). This was accompanied by a reduction in proliferation. Similar effects of NOTCH1 activation were observed in nontumoral human oligodendrocytic cells, which additionally induced strong SOX9 expression. BMP treatment reduced OLIG1/2 expression and strongly upregulated CRYAB and NOGGIN, a negative regulator of BMP. The presence of astrocyte-like SOX9<sup<+</sup< and oligodendrocyte-like OLIG1<sup<+</sup< cells in grade II IDH1-mutant gliomas raises new questions about their role in the pathology.
650		4	\|a brain tumors
650		4	\|a diffuse grade II IDH-mutant glioma
650		4	\|a diffuse IDH1-mutant gliomas
650		4	\|a cellular heterogeneity
650		4	\|a NOTCH1 pathway
650		4	\|a BMP
653		0	\|a Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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700	0		\|a Hugues Duffau \|e verfasserin \|4 aut
700	0		\|a Jean-Philippe Hugnot \|e verfasserin \|4 aut
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allfields	10.3390/cancers13092107 doi (DE-627)DOAJ001835467 (DE-599)DOAJabe2bec3c9ca426bbc7b0fc103bf0587 DE-627 ger DE-627 rakwb eng RC254-282 Meera Augustus verfasserin aut Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Diffuse grade II IDH-mutant gliomas are slow-growing brain tumors that progress into high-grade gliomas. They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell diversity is also ill-defined. Here, we report that SOX9 and OLIG1 transcription factors, which specifically label astrocytes and oligodendrocytes in the normal brain, revealed the presence of two largely nonoverlapping tumoral populations in IDH1-mutant oligodendrogliomas and astrocytomas. Astrocyte-like SOX9<sup<+</sup< cells additionally stained for APOE, CRYAB, ID4, KCNN3, while oligodendrocyte-like OLIG1<sup<+</sup< cells stained for ASCL1, EGFR, IDH1, PDGFRA, PTPRZ1, SOX4, and SOX8. GPR17, an oligodendrocytic marker, was expressed by both cells. These two subpopulations appear to have distinct BMP, NOTCH1, and MAPK active pathways as stainings for BMP4, HEY1, HEY2, p-SMAD1/5 and p-ERK were higher in SOX9<sup<+</sup< cells. We used primary cultures and a new cell line to explore the influence of NOTCH1 activation and BMP treatment on the IDH1-mutant glioma cell phenotype. This revealed that NOTCH1 globally reduced oligodendrocytic markers and IDH1 expression while upregulating <i<APOE, CRYAB, HEY1/2,</i< and an electrophysiologically-active Ca<sup<2+</sup<-activated apamin-sensitive K<sup<+</sup< channel (KCNN3/SK3). This was accompanied by a reduction in proliferation. Similar effects of NOTCH1 activation were observed in nontumoral human oligodendrocytic cells, which additionally induced strong SOX9 expression. BMP treatment reduced OLIG1/2 expression and strongly upregulated CRYAB and NOGGIN, a negative regulator of BMP. The presence of astrocyte-like SOX9<sup<+</sup< and oligodendrocyte-like OLIG1<sup<+</sup< cells in grade II IDH1-mutant gliomas raises new questions about their role in the pathology. brain tumors diffuse grade II IDH-mutant glioma diffuse IDH1-mutant gliomas cellular heterogeneity NOTCH1 pathway BMP Neoplasms. Tumors. Oncology. Including cancer and carcinogens Donovan Pineau verfasserin aut Franck Aimond verfasserin aut Safa Azar verfasserin aut Davide Lecca verfasserin aut Frédérique Scamps verfasserin aut Sophie Muxel verfasserin aut Amélie Darlix verfasserin aut William Ritchie verfasserin aut Catherine Gozé verfasserin aut Valérie Rigau verfasserin aut Hugues Duffau verfasserin aut Jean-Philippe Hugnot verfasserin aut In Cancers MDPI AG, 2010 13(2021), 9, p 2107 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:13 year:2021 number:9, p 2107 https://doi.org/10.3390/cancers13092107 kostenfrei https://doaj.org/article/abe2bec3c9ca426bbc7b0fc103bf0587 kostenfrei https://www.mdpi.com/2072-6694/13/9/2107 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_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 13 2021 9, p 2107
spelling	10.3390/cancers13092107 doi (DE-627)DOAJ001835467 (DE-599)DOAJabe2bec3c9ca426bbc7b0fc103bf0587 DE-627 ger DE-627 rakwb eng RC254-282 Meera Augustus verfasserin aut Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Diffuse grade II IDH-mutant gliomas are slow-growing brain tumors that progress into high-grade gliomas. They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell diversity is also ill-defined. Here, we report that SOX9 and OLIG1 transcription factors, which specifically label astrocytes and oligodendrocytes in the normal brain, revealed the presence of two largely nonoverlapping tumoral populations in IDH1-mutant oligodendrogliomas and astrocytomas. Astrocyte-like SOX9<sup<+</sup< cells additionally stained for APOE, CRYAB, ID4, KCNN3, while oligodendrocyte-like OLIG1<sup<+</sup< cells stained for ASCL1, EGFR, IDH1, PDGFRA, PTPRZ1, SOX4, and SOX8. GPR17, an oligodendrocytic marker, was expressed by both cells. These two subpopulations appear to have distinct BMP, NOTCH1, and MAPK active pathways as stainings for BMP4, HEY1, HEY2, p-SMAD1/5 and p-ERK were higher in SOX9<sup<+</sup< cells. We used primary cultures and a new cell line to explore the influence of NOTCH1 activation and BMP treatment on the IDH1-mutant glioma cell phenotype. This revealed that NOTCH1 globally reduced oligodendrocytic markers and IDH1 expression while upregulating <i<APOE, CRYAB, HEY1/2,</i< and an electrophysiologically-active Ca<sup<2+</sup<-activated apamin-sensitive K<sup<+</sup< channel (KCNN3/SK3). This was accompanied by a reduction in proliferation. Similar effects of NOTCH1 activation were observed in nontumoral human oligodendrocytic cells, which additionally induced strong SOX9 expression. BMP treatment reduced OLIG1/2 expression and strongly upregulated CRYAB and NOGGIN, a negative regulator of BMP. The presence of astrocyte-like SOX9<sup<+</sup< and oligodendrocyte-like OLIG1<sup<+</sup< cells in grade II IDH1-mutant gliomas raises new questions about their role in the pathology. brain tumors diffuse grade II IDH-mutant glioma diffuse IDH1-mutant gliomas cellular heterogeneity NOTCH1 pathway BMP Neoplasms. Tumors. Oncology. Including cancer and carcinogens Donovan Pineau verfasserin aut Franck Aimond verfasserin aut Safa Azar verfasserin aut Davide Lecca verfasserin aut Frédérique Scamps verfasserin aut Sophie Muxel verfasserin aut Amélie Darlix verfasserin aut William Ritchie verfasserin aut Catherine Gozé verfasserin aut Valérie Rigau verfasserin aut Hugues Duffau verfasserin aut Jean-Philippe Hugnot verfasserin aut In Cancers MDPI AG, 2010 13(2021), 9, p 2107 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:13 year:2021 number:9, p 2107 https://doi.org/10.3390/cancers13092107 kostenfrei https://doaj.org/article/abe2bec3c9ca426bbc7b0fc103bf0587 kostenfrei https://www.mdpi.com/2072-6694/13/9/2107 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_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 13 2021 9, p 2107
allfields_unstemmed	10.3390/cancers13092107 doi (DE-627)DOAJ001835467 (DE-599)DOAJabe2bec3c9ca426bbc7b0fc103bf0587 DE-627 ger DE-627 rakwb eng RC254-282 Meera Augustus verfasserin aut Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Diffuse grade II IDH-mutant gliomas are slow-growing brain tumors that progress into high-grade gliomas. They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell diversity is also ill-defined. Here, we report that SOX9 and OLIG1 transcription factors, which specifically label astrocytes and oligodendrocytes in the normal brain, revealed the presence of two largely nonoverlapping tumoral populations in IDH1-mutant oligodendrogliomas and astrocytomas. Astrocyte-like SOX9<sup<+</sup< cells additionally stained for APOE, CRYAB, ID4, KCNN3, while oligodendrocyte-like OLIG1<sup<+</sup< cells stained for ASCL1, EGFR, IDH1, PDGFRA, PTPRZ1, SOX4, and SOX8. GPR17, an oligodendrocytic marker, was expressed by both cells. These two subpopulations appear to have distinct BMP, NOTCH1, and MAPK active pathways as stainings for BMP4, HEY1, HEY2, p-SMAD1/5 and p-ERK were higher in SOX9<sup<+</sup< cells. We used primary cultures and a new cell line to explore the influence of NOTCH1 activation and BMP treatment on the IDH1-mutant glioma cell phenotype. This revealed that NOTCH1 globally reduced oligodendrocytic markers and IDH1 expression while upregulating <i<APOE, CRYAB, HEY1/2,</i< and an electrophysiologically-active Ca<sup<2+</sup<-activated apamin-sensitive K<sup<+</sup< channel (KCNN3/SK3). This was accompanied by a reduction in proliferation. Similar effects of NOTCH1 activation were observed in nontumoral human oligodendrocytic cells, which additionally induced strong SOX9 expression. BMP treatment reduced OLIG1/2 expression and strongly upregulated CRYAB and NOGGIN, a negative regulator of BMP. The presence of astrocyte-like SOX9<sup<+</sup< and oligodendrocyte-like OLIG1<sup<+</sup< cells in grade II IDH1-mutant gliomas raises new questions about their role in the pathology. brain tumors diffuse grade II IDH-mutant glioma diffuse IDH1-mutant gliomas cellular heterogeneity NOTCH1 pathway BMP Neoplasms. Tumors. Oncology. Including cancer and carcinogens Donovan Pineau verfasserin aut Franck Aimond verfasserin aut Safa Azar verfasserin aut Davide Lecca verfasserin aut Frédérique Scamps verfasserin aut Sophie Muxel verfasserin aut Amélie Darlix verfasserin aut William Ritchie verfasserin aut Catherine Gozé verfasserin aut Valérie Rigau verfasserin aut Hugues Duffau verfasserin aut Jean-Philippe Hugnot verfasserin aut In Cancers MDPI AG, 2010 13(2021), 9, p 2107 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:13 year:2021 number:9, p 2107 https://doi.org/10.3390/cancers13092107 kostenfrei https://doaj.org/article/abe2bec3c9ca426bbc7b0fc103bf0587 kostenfrei https://www.mdpi.com/2072-6694/13/9/2107 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_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 13 2021 9, p 2107
allfieldsGer	10.3390/cancers13092107 doi (DE-627)DOAJ001835467 (DE-599)DOAJabe2bec3c9ca426bbc7b0fc103bf0587 DE-627 ger DE-627 rakwb eng RC254-282 Meera Augustus verfasserin aut Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Diffuse grade II IDH-mutant gliomas are slow-growing brain tumors that progress into high-grade gliomas. They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell diversity is also ill-defined. Here, we report that SOX9 and OLIG1 transcription factors, which specifically label astrocytes and oligodendrocytes in the normal brain, revealed the presence of two largely nonoverlapping tumoral populations in IDH1-mutant oligodendrogliomas and astrocytomas. Astrocyte-like SOX9<sup<+</sup< cells additionally stained for APOE, CRYAB, ID4, KCNN3, while oligodendrocyte-like OLIG1<sup<+</sup< cells stained for ASCL1, EGFR, IDH1, PDGFRA, PTPRZ1, SOX4, and SOX8. GPR17, an oligodendrocytic marker, was expressed by both cells. These two subpopulations appear to have distinct BMP, NOTCH1, and MAPK active pathways as stainings for BMP4, HEY1, HEY2, p-SMAD1/5 and p-ERK were higher in SOX9<sup<+</sup< cells. We used primary cultures and a new cell line to explore the influence of NOTCH1 activation and BMP treatment on the IDH1-mutant glioma cell phenotype. This revealed that NOTCH1 globally reduced oligodendrocytic markers and IDH1 expression while upregulating <i<APOE, CRYAB, HEY1/2,</i< and an electrophysiologically-active Ca<sup<2+</sup<-activated apamin-sensitive K<sup<+</sup< channel (KCNN3/SK3). This was accompanied by a reduction in proliferation. Similar effects of NOTCH1 activation were observed in nontumoral human oligodendrocytic cells, which additionally induced strong SOX9 expression. BMP treatment reduced OLIG1/2 expression and strongly upregulated CRYAB and NOGGIN, a negative regulator of BMP. The presence of astrocyte-like SOX9<sup<+</sup< and oligodendrocyte-like OLIG1<sup<+</sup< cells in grade II IDH1-mutant gliomas raises new questions about their role in the pathology. brain tumors diffuse grade II IDH-mutant glioma diffuse IDH1-mutant gliomas cellular heterogeneity NOTCH1 pathway BMP Neoplasms. Tumors. Oncology. Including cancer and carcinogens Donovan Pineau verfasserin aut Franck Aimond verfasserin aut Safa Azar verfasserin aut Davide Lecca verfasserin aut Frédérique Scamps verfasserin aut Sophie Muxel verfasserin aut Amélie Darlix verfasserin aut William Ritchie verfasserin aut Catherine Gozé verfasserin aut Valérie Rigau verfasserin aut Hugues Duffau verfasserin aut Jean-Philippe Hugnot verfasserin aut In Cancers MDPI AG, 2010 13(2021), 9, p 2107 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:13 year:2021 number:9, p 2107 https://doi.org/10.3390/cancers13092107 kostenfrei https://doaj.org/article/abe2bec3c9ca426bbc7b0fc103bf0587 kostenfrei https://www.mdpi.com/2072-6694/13/9/2107 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_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 13 2021 9, p 2107
allfieldsSound	10.3390/cancers13092107 doi (DE-627)DOAJ001835467 (DE-599)DOAJabe2bec3c9ca426bbc7b0fc103bf0587 DE-627 ger DE-627 rakwb eng RC254-282 Meera Augustus verfasserin aut Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Diffuse grade II IDH-mutant gliomas are slow-growing brain tumors that progress into high-grade gliomas. They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell diversity is also ill-defined. Here, we report that SOX9 and OLIG1 transcription factors, which specifically label astrocytes and oligodendrocytes in the normal brain, revealed the presence of two largely nonoverlapping tumoral populations in IDH1-mutant oligodendrogliomas and astrocytomas. Astrocyte-like SOX9<sup<+</sup< cells additionally stained for APOE, CRYAB, ID4, KCNN3, while oligodendrocyte-like OLIG1<sup<+</sup< cells stained for ASCL1, EGFR, IDH1, PDGFRA, PTPRZ1, SOX4, and SOX8. GPR17, an oligodendrocytic marker, was expressed by both cells. These two subpopulations appear to have distinct BMP, NOTCH1, and MAPK active pathways as stainings for BMP4, HEY1, HEY2, p-SMAD1/5 and p-ERK were higher in SOX9<sup<+</sup< cells. We used primary cultures and a new cell line to explore the influence of NOTCH1 activation and BMP treatment on the IDH1-mutant glioma cell phenotype. This revealed that NOTCH1 globally reduced oligodendrocytic markers and IDH1 expression while upregulating <i<APOE, CRYAB, HEY1/2,</i< and an electrophysiologically-active Ca<sup<2+</sup<-activated apamin-sensitive K<sup<+</sup< channel (KCNN3/SK3). This was accompanied by a reduction in proliferation. Similar effects of NOTCH1 activation were observed in nontumoral human oligodendrocytic cells, which additionally induced strong SOX9 expression. BMP treatment reduced OLIG1/2 expression and strongly upregulated CRYAB and NOGGIN, a negative regulator of BMP. The presence of astrocyte-like SOX9<sup<+</sup< and oligodendrocyte-like OLIG1<sup<+</sup< cells in grade II IDH1-mutant gliomas raises new questions about their role in the pathology. brain tumors diffuse grade II IDH-mutant glioma diffuse IDH1-mutant gliomas cellular heterogeneity NOTCH1 pathway BMP Neoplasms. Tumors. Oncology. Including cancer and carcinogens Donovan Pineau verfasserin aut Franck Aimond verfasserin aut Safa Azar verfasserin aut Davide Lecca verfasserin aut Frédérique Scamps verfasserin aut Sophie Muxel verfasserin aut Amélie Darlix verfasserin aut William Ritchie verfasserin aut Catherine Gozé verfasserin aut Valérie Rigau verfasserin aut Hugues Duffau verfasserin aut Jean-Philippe Hugnot verfasserin aut In Cancers MDPI AG, 2010 13(2021), 9, p 2107 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:13 year:2021 number:9, p 2107 https://doi.org/10.3390/cancers13092107 kostenfrei https://doaj.org/article/abe2bec3c9ca426bbc7b0fc103bf0587 kostenfrei https://www.mdpi.com/2072-6694/13/9/2107 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_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 13 2021 9, p 2107
language	English
source	In Cancers 13(2021), 9, p 2107 volume:13 year:2021 number:9, p 2107
sourceStr	In Cancers 13(2021), 9, p 2107 volume:13 year:2021 number:9, p 2107
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	brain tumors diffuse grade II IDH-mutant glioma diffuse IDH1-mutant gliomas cellular heterogeneity NOTCH1 pathway BMP Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Cancers
authorswithroles_txt_mv	Meera Augustus @@aut@@ Donovan Pineau @@aut@@ Franck Aimond @@aut@@ Safa Azar @@aut@@ Davide Lecca @@aut@@ Frédérique Scamps @@aut@@ Sophie Muxel @@aut@@ Amélie Darlix @@aut@@ William Ritchie @@aut@@ Catherine Gozé @@aut@@ Valérie Rigau @@aut@@ Hugues Duffau @@aut@@ Jean-Philippe Hugnot @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	614095670
id	DOAJ001835467
language_de	englisch
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callnumber-first	R - Medicine
author	Meera Augustus
spellingShingle	Meera Augustus misc RC254-282 misc brain tumors misc diffuse grade II IDH-mutant glioma misc diffuse IDH1-mutant gliomas misc cellular heterogeneity misc NOTCH1 pathway misc BMP misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis
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topic_title	RC254-282 Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis brain tumors diffuse grade II IDH-mutant glioma diffuse IDH1-mutant gliomas cellular heterogeneity NOTCH1 pathway BMP
topic	misc RC254-282 misc brain tumors misc diffuse grade II IDH-mutant glioma misc diffuse IDH1-mutant gliomas misc cellular heterogeneity misc NOTCH1 pathway misc BMP misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc brain tumors misc diffuse grade II IDH-mutant glioma misc diffuse IDH1-mutant gliomas misc cellular heterogeneity misc NOTCH1 pathway misc BMP misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc brain tumors misc diffuse grade II IDH-mutant glioma misc diffuse IDH1-mutant gliomas misc cellular heterogeneity misc NOTCH1 pathway misc BMP misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis
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title_full	Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis
author_sort	Meera Augustus
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author_browse	Meera Augustus Donovan Pineau Franck Aimond Safa Azar Davide Lecca Frédérique Scamps Sophie Muxel Amélie Darlix William Ritchie Catherine Gozé Valérie Rigau Hugues Duffau Jean-Philippe Hugnot
container_volume	13
class	RC254-282
format_se	Elektronische Aufsätze
author-letter	Meera Augustus
doi_str_mv	10.3390/cancers13092107
author2-role	verfasserin
title_sort	identification of cryab<sup<+</sup< kcnn3<sup<+</sup< sox9<sup<+</sup< astrocyte-like and egfr<sup<+</sup< pdgfra<sup<+</sup< olig1<sup<+</sup< oligodendrocyte-like tumoral cells in diffuse idh1-mutant gliomas and implication of notch1 signalling in their genesis
callnumber	RC254-282
title_auth	Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis
abstract	Diffuse grade II IDH-mutant gliomas are slow-growing brain tumors that progress into high-grade gliomas. They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell diversity is also ill-defined. Here, we report that SOX9 and OLIG1 transcription factors, which specifically label astrocytes and oligodendrocytes in the normal brain, revealed the presence of two largely nonoverlapping tumoral populations in IDH1-mutant oligodendrogliomas and astrocytomas. Astrocyte-like SOX9<sup<+</sup< cells additionally stained for APOE, CRYAB, ID4, KCNN3, while oligodendrocyte-like OLIG1<sup<+</sup< cells stained for ASCL1, EGFR, IDH1, PDGFRA, PTPRZ1, SOX4, and SOX8. GPR17, an oligodendrocytic marker, was expressed by both cells. These two subpopulations appear to have distinct BMP, NOTCH1, and MAPK active pathways as stainings for BMP4, HEY1, HEY2, p-SMAD1/5 and p-ERK were higher in SOX9<sup<+</sup< cells. We used primary cultures and a new cell line to explore the influence of NOTCH1 activation and BMP treatment on the IDH1-mutant glioma cell phenotype. This revealed that NOTCH1 globally reduced oligodendrocytic markers and IDH1 expression while upregulating <i<APOE, CRYAB, HEY1/2,</i< and an electrophysiologically-active Ca<sup<2+</sup<-activated apamin-sensitive K<sup<+</sup< channel (KCNN3/SK3). This was accompanied by a reduction in proliferation. Similar effects of NOTCH1 activation were observed in nontumoral human oligodendrocytic cells, which additionally induced strong SOX9 expression. BMP treatment reduced OLIG1/2 expression and strongly upregulated CRYAB and NOGGIN, a negative regulator of BMP. The presence of astrocyte-like SOX9<sup<+</sup< and oligodendrocyte-like OLIG1<sup<+</sup< cells in grade II IDH1-mutant gliomas raises new questions about their role in the pathology.
abstractGer	Diffuse grade II IDH-mutant gliomas are slow-growing brain tumors that progress into high-grade gliomas. They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell diversity is also ill-defined. Here, we report that SOX9 and OLIG1 transcription factors, which specifically label astrocytes and oligodendrocytes in the normal brain, revealed the presence of two largely nonoverlapping tumoral populations in IDH1-mutant oligodendrogliomas and astrocytomas. Astrocyte-like SOX9<sup<+</sup< cells additionally stained for APOE, CRYAB, ID4, KCNN3, while oligodendrocyte-like OLIG1<sup<+</sup< cells stained for ASCL1, EGFR, IDH1, PDGFRA, PTPRZ1, SOX4, and SOX8. GPR17, an oligodendrocytic marker, was expressed by both cells. These two subpopulations appear to have distinct BMP, NOTCH1, and MAPK active pathways as stainings for BMP4, HEY1, HEY2, p-SMAD1/5 and p-ERK were higher in SOX9<sup<+</sup< cells. We used primary cultures and a new cell line to explore the influence of NOTCH1 activation and BMP treatment on the IDH1-mutant glioma cell phenotype. This revealed that NOTCH1 globally reduced oligodendrocytic markers and IDH1 expression while upregulating <i<APOE, CRYAB, HEY1/2,</i< and an electrophysiologically-active Ca<sup<2+</sup<-activated apamin-sensitive K<sup<+</sup< channel (KCNN3/SK3). This was accompanied by a reduction in proliferation. Similar effects of NOTCH1 activation were observed in nontumoral human oligodendrocytic cells, which additionally induced strong SOX9 expression. BMP treatment reduced OLIG1/2 expression and strongly upregulated CRYAB and NOGGIN, a negative regulator of BMP. The presence of astrocyte-like SOX9<sup<+</sup< and oligodendrocyte-like OLIG1<sup<+</sup< cells in grade II IDH1-mutant gliomas raises new questions about their role in the pathology.
abstract_unstemmed	Diffuse grade II IDH-mutant gliomas are slow-growing brain tumors that progress into high-grade gliomas. They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell diversity is also ill-defined. Here, we report that SOX9 and OLIG1 transcription factors, which specifically label astrocytes and oligodendrocytes in the normal brain, revealed the presence of two largely nonoverlapping tumoral populations in IDH1-mutant oligodendrogliomas and astrocytomas. Astrocyte-like SOX9<sup<+</sup< cells additionally stained for APOE, CRYAB, ID4, KCNN3, while oligodendrocyte-like OLIG1<sup<+</sup< cells stained for ASCL1, EGFR, IDH1, PDGFRA, PTPRZ1, SOX4, and SOX8. GPR17, an oligodendrocytic marker, was expressed by both cells. These two subpopulations appear to have distinct BMP, NOTCH1, and MAPK active pathways as stainings for BMP4, HEY1, HEY2, p-SMAD1/5 and p-ERK were higher in SOX9<sup<+</sup< cells. We used primary cultures and a new cell line to explore the influence of NOTCH1 activation and BMP treatment on the IDH1-mutant glioma cell phenotype. This revealed that NOTCH1 globally reduced oligodendrocytic markers and IDH1 expression while upregulating <i<APOE, CRYAB, HEY1/2,</i< and an electrophysiologically-active Ca<sup<2+</sup<-activated apamin-sensitive K<sup<+</sup< channel (KCNN3/SK3). This was accompanied by a reduction in proliferation. Similar effects of NOTCH1 activation were observed in nontumoral human oligodendrocytic cells, which additionally induced strong SOX9 expression. BMP treatment reduced OLIG1/2 expression and strongly upregulated CRYAB and NOGGIN, a negative regulator of BMP. The presence of astrocyte-like SOX9<sup<+</sup< and oligodendrocyte-like OLIG1<sup<+</sup< cells in grade II IDH1-mutant gliomas raises new questions about their role in the pathology.
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title_short	Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis
url	https://doi.org/10.3390/cancers13092107 https://doaj.org/article/abe2bec3c9ca426bbc7b0fc103bf0587 https://www.mdpi.com/2072-6694/13/9/2107 https://doaj.org/toc/2072-6694
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They present intratumoral cell heterogeneity, and no reliable markers are available to distinguish the different cell subtypes. The molecular mechanisms underlying the formation of this cell diversity is also ill-defined. Here, we report that SOX9 and OLIG1 transcription factors, which specifically label astrocytes and oligodendrocytes in the normal brain, revealed the presence of two largely nonoverlapping tumoral populations in IDH1-mutant oligodendrogliomas and astrocytomas. Astrocyte-like SOX9<sup<+</sup< cells additionally stained for APOE, CRYAB, ID4, KCNN3, while oligodendrocyte-like OLIG1<sup<+</sup< cells stained for ASCL1, EGFR, IDH1, PDGFRA, PTPRZ1, SOX4, and SOX8. GPR17, an oligodendrocytic marker, was expressed by both cells. These two subpopulations appear to have distinct BMP, NOTCH1, and MAPK active pathways as stainings for BMP4, HEY1, HEY2, p-SMAD1/5 and p-ERK were higher in SOX9<sup<+</sup< cells. We used primary cultures and a new cell line to explore the influence of NOTCH1 activation and BMP treatment on the IDH1-mutant glioma cell phenotype. This revealed that NOTCH1 globally reduced oligodendrocytic markers and IDH1 expression while upregulating <i<APOE, CRYAB, HEY1/2,</i< and an electrophysiologically-active Ca<sup<2+</sup<-activated apamin-sensitive K<sup<+</sup< channel (KCNN3/SK3). This was accompanied by a reduction in proliferation. Similar effects of NOTCH1 activation were observed in nontumoral human oligodendrocytic cells, which additionally induced strong SOX9 expression. BMP treatment reduced OLIG1/2 expression and strongly upregulated CRYAB and NOGGIN, a negative regulator of BMP. 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Identification of CRYAB<sup<+</sup< KCNN3<sup<+</sup< SOX9<sup<+</sup< Astrocyte-Like and EGFR<sup<+</sup< PDGFRA<sup<+</sup< OLIG1<sup<+</sup< Oligodendrocyte-Like Tumoral Cells in Diffuse IDH1-Mutant Gliomas and Implication of NOTCH1 Signalling in Their Genesis

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