An environment-dependent transcriptional network specifies human microglia identity

Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microg...
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Autor*in:	Gosselin, David [verfasserIn] Skola, Dylan Coufal, Nicole G Holtman, Inge R Schlachetzki, Johannes C. M Sajti, Eniko Jaeger, Baptiste N O'Connor, Carolyn Fitzpatrick, Conor Pasillas, Martina P Pena, Monique Adair, Amy Gonda, David D Levy, Michael L Ransohoff, Richard M Gage, Fred H Glass, Christopher K

Format:	Artikel
Sprache:	Englisch

Erschienen:	2017

Rechteinformationen:	Nutzungsrecht: © info:eu-repo/semantics/closedAccess

Übergeordnetes Werk:	Enthalten in: Science - Washington, DC : AAAS, American Assoc. for the Advancement of Science, 1883, 356(2017), 6344, Seite 1248-+
Übergeordnetes Werk:	volume:356 ; year:2017 ; number:6344 ; pages:1248-+

Links:	Link aufrufen

Katalog-ID:	OLC1997363887

Internformat


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520			\|a Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases.
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Indexfelder

author_variant	d g dg
matchkey_str	article:00368075:2017----::nniomndpnetrncitoantokpcfeh
hierarchy_sort_str	2017
publishDate	2017
allfields	PQ20171125 (DE-627)OLC1997363887 (DE-599)GBVOLC1997363887 (PRQ)n1781-10a5900da65d4554b133db87f89ac911e0ed70d6c63214be5344022537f1a4cf0 (KEY)0063888920170000356634401248environmentdependenttranscriptionalnetworkspecifie DE-627 ger DE-627 rakwb eng 500 DE-600 LING fid Gosselin, David verfasserin aut An environment-dependent transcriptional network specifies human microglia identity 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases. Nutzungsrecht: © info:eu-repo/semantics/closedAccess Skola, Dylan oth Coufal, Nicole G oth Holtman, Inge R oth Schlachetzki, Johannes C. M oth Sajti, Eniko oth Jaeger, Baptiste N oth O'Connor, Carolyn oth Fitzpatrick, Conor oth Pasillas, Martina P oth Pena, Monique oth Adair, Amy oth Gonda, David D oth Levy, Michael L oth Ransohoff, Richard M oth Gage, Fred H oth Glass, Christopher K oth Enthalten in Science Washington, DC : AAAS, American Assoc. for the Advancement of Science, 1883 356(2017), 6344, Seite 1248-+ (DE-627)12931482X (DE-600)128410-1 (DE-576)014533189 0036-8075 nnns volume:356 year:2017 number:6344 pages:1248-+ http://www.narcis.nl/publication/RecordID/oai:pure.rug.nl:publications%2Fe10ef9c9-e902-4e32-964b-48291e50099b GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-IBL SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_20 GBV_ILN_21 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_92 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_131 GBV_ILN_170 GBV_ILN_171 GBV_ILN_179 GBV_ILN_181 GBV_ILN_211 GBV_ILN_252 GBV_ILN_259 GBV_ILN_290 GBV_ILN_600 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2012 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4036 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4310 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4318 GBV_ILN_4320 GBV_ILN_4328 GBV_ILN_4333 AR 356 2017 6344 1248-+
spelling	PQ20171125 (DE-627)OLC1997363887 (DE-599)GBVOLC1997363887 (PRQ)n1781-10a5900da65d4554b133db87f89ac911e0ed70d6c63214be5344022537f1a4cf0 (KEY)0063888920170000356634401248environmentdependenttranscriptionalnetworkspecifie DE-627 ger DE-627 rakwb eng 500 DE-600 LING fid Gosselin, David verfasserin aut An environment-dependent transcriptional network specifies human microglia identity 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases. Nutzungsrecht: © info:eu-repo/semantics/closedAccess Skola, Dylan oth Coufal, Nicole G oth Holtman, Inge R oth Schlachetzki, Johannes C. M oth Sajti, Eniko oth Jaeger, Baptiste N oth O'Connor, Carolyn oth Fitzpatrick, Conor oth Pasillas, Martina P oth Pena, Monique oth Adair, Amy oth Gonda, David D oth Levy, Michael L oth Ransohoff, Richard M oth Gage, Fred H oth Glass, Christopher K oth Enthalten in Science Washington, DC : AAAS, American Assoc. for the Advancement of Science, 1883 356(2017), 6344, Seite 1248-+ (DE-627)12931482X (DE-600)128410-1 (DE-576)014533189 0036-8075 nnns volume:356 year:2017 number:6344 pages:1248-+ http://www.narcis.nl/publication/RecordID/oai:pure.rug.nl:publications%2Fe10ef9c9-e902-4e32-964b-48291e50099b GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-IBL SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_20 GBV_ILN_21 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_92 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_131 GBV_ILN_170 GBV_ILN_171 GBV_ILN_179 GBV_ILN_181 GBV_ILN_211 GBV_ILN_252 GBV_ILN_259 GBV_ILN_290 GBV_ILN_600 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2012 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4036 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4310 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4318 GBV_ILN_4320 GBV_ILN_4328 GBV_ILN_4333 AR 356 2017 6344 1248-+
allfields_unstemmed	PQ20171125 (DE-627)OLC1997363887 (DE-599)GBVOLC1997363887 (PRQ)n1781-10a5900da65d4554b133db87f89ac911e0ed70d6c63214be5344022537f1a4cf0 (KEY)0063888920170000356634401248environmentdependenttranscriptionalnetworkspecifie DE-627 ger DE-627 rakwb eng 500 DE-600 LING fid Gosselin, David verfasserin aut An environment-dependent transcriptional network specifies human microglia identity 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases. Nutzungsrecht: © info:eu-repo/semantics/closedAccess Skola, Dylan oth Coufal, Nicole G oth Holtman, Inge R oth Schlachetzki, Johannes C. M oth Sajti, Eniko oth Jaeger, Baptiste N oth O'Connor, Carolyn oth Fitzpatrick, Conor oth Pasillas, Martina P oth Pena, Monique oth Adair, Amy oth Gonda, David D oth Levy, Michael L oth Ransohoff, Richard M oth Gage, Fred H oth Glass, Christopher K oth Enthalten in Science Washington, DC : AAAS, American Assoc. for the Advancement of Science, 1883 356(2017), 6344, Seite 1248-+ (DE-627)12931482X (DE-600)128410-1 (DE-576)014533189 0036-8075 nnns volume:356 year:2017 number:6344 pages:1248-+ http://www.narcis.nl/publication/RecordID/oai:pure.rug.nl:publications%2Fe10ef9c9-e902-4e32-964b-48291e50099b GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-IBL SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_20 GBV_ILN_21 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_92 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_131 GBV_ILN_170 GBV_ILN_171 GBV_ILN_179 GBV_ILN_181 GBV_ILN_211 GBV_ILN_252 GBV_ILN_259 GBV_ILN_290 GBV_ILN_600 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2012 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4036 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4310 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4318 GBV_ILN_4320 GBV_ILN_4328 GBV_ILN_4333 AR 356 2017 6344 1248-+
allfieldsGer	PQ20171125 (DE-627)OLC1997363887 (DE-599)GBVOLC1997363887 (PRQ)n1781-10a5900da65d4554b133db87f89ac911e0ed70d6c63214be5344022537f1a4cf0 (KEY)0063888920170000356634401248environmentdependenttranscriptionalnetworkspecifie DE-627 ger DE-627 rakwb eng 500 DE-600 LING fid Gosselin, David verfasserin aut An environment-dependent transcriptional network specifies human microglia identity 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases. Nutzungsrecht: © info:eu-repo/semantics/closedAccess Skola, Dylan oth Coufal, Nicole G oth Holtman, Inge R oth Schlachetzki, Johannes C. M oth Sajti, Eniko oth Jaeger, Baptiste N oth O'Connor, Carolyn oth Fitzpatrick, Conor oth Pasillas, Martina P oth Pena, Monique oth Adair, Amy oth Gonda, David D oth Levy, Michael L oth Ransohoff, Richard M oth Gage, Fred H oth Glass, Christopher K oth Enthalten in Science Washington, DC : AAAS, American Assoc. for the Advancement of Science, 1883 356(2017), 6344, Seite 1248-+ (DE-627)12931482X (DE-600)128410-1 (DE-576)014533189 0036-8075 nnns volume:356 year:2017 number:6344 pages:1248-+ http://www.narcis.nl/publication/RecordID/oai:pure.rug.nl:publications%2Fe10ef9c9-e902-4e32-964b-48291e50099b GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-IBL SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_20 GBV_ILN_21 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_92 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_131 GBV_ILN_170 GBV_ILN_171 GBV_ILN_179 GBV_ILN_181 GBV_ILN_211 GBV_ILN_252 GBV_ILN_259 GBV_ILN_290 GBV_ILN_600 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2012 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4036 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4310 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4318 GBV_ILN_4320 GBV_ILN_4328 GBV_ILN_4333 AR 356 2017 6344 1248-+
allfieldsSound	PQ20171125 (DE-627)OLC1997363887 (DE-599)GBVOLC1997363887 (PRQ)n1781-10a5900da65d4554b133db87f89ac911e0ed70d6c63214be5344022537f1a4cf0 (KEY)0063888920170000356634401248environmentdependenttranscriptionalnetworkspecifie DE-627 ger DE-627 rakwb eng 500 DE-600 LING fid Gosselin, David verfasserin aut An environment-dependent transcriptional network specifies human microglia identity 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases. Nutzungsrecht: © info:eu-repo/semantics/closedAccess Skola, Dylan oth Coufal, Nicole G oth Holtman, Inge R oth Schlachetzki, Johannes C. M oth Sajti, Eniko oth Jaeger, Baptiste N oth O'Connor, Carolyn oth Fitzpatrick, Conor oth Pasillas, Martina P oth Pena, Monique oth Adair, Amy oth Gonda, David D oth Levy, Michael L oth Ransohoff, Richard M oth Gage, Fred H oth Glass, Christopher K oth Enthalten in Science Washington, DC : AAAS, American Assoc. for the Advancement of Science, 1883 356(2017), 6344, Seite 1248-+ (DE-627)12931482X (DE-600)128410-1 (DE-576)014533189 0036-8075 nnns volume:356 year:2017 number:6344 pages:1248-+ http://www.narcis.nl/publication/RecordID/oai:pure.rug.nl:publications%2Fe10ef9c9-e902-4e32-964b-48291e50099b GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-IBL SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_20 GBV_ILN_21 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_92 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_131 GBV_ILN_170 GBV_ILN_171 GBV_ILN_179 GBV_ILN_181 GBV_ILN_211 GBV_ILN_252 GBV_ILN_259 GBV_ILN_290 GBV_ILN_600 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2012 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4036 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4310 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4318 GBV_ILN_4320 GBV_ILN_4328 GBV_ILN_4333 AR 356 2017 6344 1248-+
language	English
source	Enthalten in Science 356(2017), 6344, Seite 1248-+ volume:356 year:2017 number:6344 pages:1248-+
sourceStr	Enthalten in Science 356(2017), 6344, Seite 1248-+ volume:356 year:2017 number:6344 pages:1248-+
format_phy_str_mv	Article
institution	findex.gbv.de
dewey-raw	500
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container_title	Science
authorswithroles_txt_mv	Gosselin, David @@aut@@ Skola, Dylan @@oth@@ Coufal, Nicole G @@oth@@ Holtman, Inge R @@oth@@ Schlachetzki, Johannes C. M @@oth@@ Sajti, Eniko @@oth@@ Jaeger, Baptiste N @@oth@@ O'Connor, Carolyn @@oth@@ Fitzpatrick, Conor @@oth@@ Pasillas, Martina P @@oth@@ Pena, Monique @@oth@@ Adair, Amy @@oth@@ Gonda, David D @@oth@@ Levy, Michael L @@oth@@ Ransohoff, Richard M @@oth@@ Gage, Fred H @@oth@@ Glass, Christopher K @@oth@@
publishDateDaySort_date	2017-01-01T00:00:00Z
hierarchy_top_id	12931482X
dewey-sort	3500
id	OLC1997363887
language_de	englisch
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title	An environment-dependent transcriptional network specifies human microglia identity
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title_sort	environment-dependent transcriptional network specifies human microglia identity
title_auth	An environment-dependent transcriptional network specifies human microglia identity
abstract	Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases.
abstractGer	Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases.
abstract_unstemmed	Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases.
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title_short	An environment-dependent transcriptional network specifies human microglia identity
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