Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells

Background Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neuro...
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Autor*in:	Zhou, Qiong [verfasserIn] Viollet, Coralie Efthymiou, Anastasia Khayrullina, Guzal Moritz, Kasey E. Wilkerson, Matthew D. Sukumar, Gauthaman Dalgard, Clifton L. Doughty, Martin L.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Human induced pluripotent stem cell Astrocyte RNA sequencing Glutamate uptake Phagocytosis

Anmerkung:	© The Author(s). 2019

Übergeordnetes Werk:	Enthalten in: Journal of neuroinflammation - London : BioMed Central, 2004, 16(2019), 1 vom: 09. Aug.
Übergeordnetes Werk:	volume:16 ; year:2019 ; number:1 ; day:09 ; month:08

Links:	Volltext

DOI / URN:	10.1186/s12974-019-1553-x

Katalog-ID:	SPR029114926

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520			\|a Background Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). Methods Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1β (interleukin-1 beta). Results We show TNFα and IL-1β induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1β effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. Conclusion Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes.
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allfields	10.1186/s12974-019-1553-x doi (DE-627)SPR029114926 (SPR)s12974-019-1553-x-e DE-627 ger DE-627 rakwb eng Zhou, Qiong verfasserin aut Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). Methods Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1β (interleukin-1 beta). Results We show TNFα and IL-1β induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1β effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. Conclusion Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes. Human induced pluripotent stem cell (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 RNA sequencing (dpeaa)DE-He213 Glutamate uptake (dpeaa)DE-He213 Phagocytosis (dpeaa)DE-He213 Viollet, Coralie aut Efthymiou, Anastasia aut Khayrullina, Guzal aut Moritz, Kasey E. aut Wilkerson, Matthew D. aut Sukumar, Gauthaman aut Dalgard, Clifton L. aut Doughty, Martin L. (orcid)0000-0002-2931-6426 aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 16(2019), 1 vom: 09. Aug. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:16 year:2019 number:1 day:09 month:08 https://dx.doi.org/10.1186/s12974-019-1553-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 16 2019 1 09 08
spelling	10.1186/s12974-019-1553-x doi (DE-627)SPR029114926 (SPR)s12974-019-1553-x-e DE-627 ger DE-627 rakwb eng Zhou, Qiong verfasserin aut Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). Methods Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1β (interleukin-1 beta). Results We show TNFα and IL-1β induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1β effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. Conclusion Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes. Human induced pluripotent stem cell (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 RNA sequencing (dpeaa)DE-He213 Glutamate uptake (dpeaa)DE-He213 Phagocytosis (dpeaa)DE-He213 Viollet, Coralie aut Efthymiou, Anastasia aut Khayrullina, Guzal aut Moritz, Kasey E. aut Wilkerson, Matthew D. aut Sukumar, Gauthaman aut Dalgard, Clifton L. aut Doughty, Martin L. (orcid)0000-0002-2931-6426 aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 16(2019), 1 vom: 09. Aug. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:16 year:2019 number:1 day:09 month:08 https://dx.doi.org/10.1186/s12974-019-1553-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 16 2019 1 09 08
allfields_unstemmed	10.1186/s12974-019-1553-x doi (DE-627)SPR029114926 (SPR)s12974-019-1553-x-e DE-627 ger DE-627 rakwb eng Zhou, Qiong verfasserin aut Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). Methods Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1β (interleukin-1 beta). Results We show TNFα and IL-1β induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1β effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. Conclusion Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes. Human induced pluripotent stem cell (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 RNA sequencing (dpeaa)DE-He213 Glutamate uptake (dpeaa)DE-He213 Phagocytosis (dpeaa)DE-He213 Viollet, Coralie aut Efthymiou, Anastasia aut Khayrullina, Guzal aut Moritz, Kasey E. aut Wilkerson, Matthew D. aut Sukumar, Gauthaman aut Dalgard, Clifton L. aut Doughty, Martin L. (orcid)0000-0002-2931-6426 aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 16(2019), 1 vom: 09. Aug. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:16 year:2019 number:1 day:09 month:08 https://dx.doi.org/10.1186/s12974-019-1553-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 16 2019 1 09 08
allfieldsGer	10.1186/s12974-019-1553-x doi (DE-627)SPR029114926 (SPR)s12974-019-1553-x-e DE-627 ger DE-627 rakwb eng Zhou, Qiong verfasserin aut Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). Methods Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1β (interleukin-1 beta). Results We show TNFα and IL-1β induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1β effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. Conclusion Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes. Human induced pluripotent stem cell (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 RNA sequencing (dpeaa)DE-He213 Glutamate uptake (dpeaa)DE-He213 Phagocytosis (dpeaa)DE-He213 Viollet, Coralie aut Efthymiou, Anastasia aut Khayrullina, Guzal aut Moritz, Kasey E. aut Wilkerson, Matthew D. aut Sukumar, Gauthaman aut Dalgard, Clifton L. aut Doughty, Martin L. (orcid)0000-0002-2931-6426 aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 16(2019), 1 vom: 09. Aug. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:16 year:2019 number:1 day:09 month:08 https://dx.doi.org/10.1186/s12974-019-1553-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 16 2019 1 09 08
allfieldsSound	10.1186/s12974-019-1553-x doi (DE-627)SPR029114926 (SPR)s12974-019-1553-x-e DE-627 ger DE-627 rakwb eng Zhou, Qiong verfasserin aut Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). Methods Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1β (interleukin-1 beta). Results We show TNFα and IL-1β induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1β effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. Conclusion Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes. Human induced pluripotent stem cell (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 RNA sequencing (dpeaa)DE-He213 Glutamate uptake (dpeaa)DE-He213 Phagocytosis (dpeaa)DE-He213 Viollet, Coralie aut Efthymiou, Anastasia aut Khayrullina, Guzal aut Moritz, Kasey E. aut Wilkerson, Matthew D. aut Sukumar, Gauthaman aut Dalgard, Clifton L. aut Doughty, Martin L. (orcid)0000-0002-2931-6426 aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 16(2019), 1 vom: 09. Aug. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:16 year:2019 number:1 day:09 month:08 https://dx.doi.org/10.1186/s12974-019-1553-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 16 2019 1 09 08
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topic_facet	Human induced pluripotent stem cell Astrocyte RNA sequencing Glutamate uptake Phagocytosis
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author	Zhou, Qiong
spellingShingle	Zhou, Qiong misc Human induced pluripotent stem cell misc Astrocyte misc RNA sequencing misc Glutamate uptake misc Phagocytosis Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells
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topic_title	Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells Human induced pluripotent stem cell (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 RNA sequencing (dpeaa)DE-He213 Glutamate uptake (dpeaa)DE-He213 Phagocytosis (dpeaa)DE-He213
topic	misc Human induced pluripotent stem cell misc Astrocyte misc RNA sequencing misc Glutamate uptake misc Phagocytosis
topic_unstemmed	misc Human induced pluripotent stem cell misc Astrocyte misc RNA sequencing misc Glutamate uptake misc Phagocytosis
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title	Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells
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title_full	Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells
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author_browse	Zhou, Qiong Viollet, Coralie Efthymiou, Anastasia Khayrullina, Guzal Moritz, Kasey E. Wilkerson, Matthew D. Sukumar, Gauthaman Dalgard, Clifton L. Doughty, Martin L.
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title_sort	neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells
title_auth	Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells
abstract	Background Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). Methods Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1β (interleukin-1 beta). Results We show TNFα and IL-1β induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1β effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. Conclusion Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes. © The Author(s). 2019
abstractGer	Background Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). Methods Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1β (interleukin-1 beta). Results We show TNFα and IL-1β induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1β effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. Conclusion Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes. © The Author(s). 2019
abstract_unstemmed	Background Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). Methods Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1β (interleukin-1 beta). Results We show TNFα and IL-1β induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1β effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. Conclusion Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes. © The Author(s). 2019
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title_short	Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells
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author2	Viollet, Coralie Efthymiou, Anastasia Khayrullina, Guzal Moritz, Kasey E. Wilkerson, Matthew D. Sukumar, Gauthaman Dalgard, Clifton L. Doughty, Martin L.
author2Str	Viollet, Coralie Efthymiou, Anastasia Khayrullina, Guzal Moritz, Kasey E. Wilkerson, Matthew D. Sukumar, Gauthaman Dalgard, Clifton L. Doughty, Martin L.
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up_date	2024-07-03T23:33:04.212Z
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Conclusion Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. 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Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells

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