Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.7/415 |
Resumo: | The gene regulatory network (GRN) that supports neural stem cell (NS cell) self-renewal has so far been poorly characterized. Knowledge of the central transcription factors (TFs), the noncoding gene regulatory regions that they bind to, and the genes whose expression they modulate will be crucial in unlocking the full therapeutic potential of these cells. Here, we use DNase-seq in combination with analysis of histone modifications to identify multiple classes of epigenetically and functionally distinct cis-regulatory elements (CREs). Through motif analysis and ChIP-seq, we identify several of the crucial TF regulators of NS cells. At the core of the network are TFs of the basic helix-loop-helix (bHLH), nuclear factor I (NFI), SOX, and FOX families, with CREs often densely bound by several of these different TFs. We use machine learning to highlight several crucial regulatory features of the network that underpin NS cell self-renewal and multipotency. We validate our predictions by functional analysis of the bHLH TF OLIG2. This TF makes an important contribution to NS cell self-renewal by concurrently activating pro-proliferation genes and preventing the untimely activation of genes promoting neuronal differentiation and stem cell quiescence. |
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Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewalStem CellsOLIG2The gene regulatory network (GRN) that supports neural stem cell (NS cell) self-renewal has so far been poorly characterized. Knowledge of the central transcription factors (TFs), the noncoding gene regulatory regions that they bind to, and the genes whose expression they modulate will be crucial in unlocking the full therapeutic potential of these cells. Here, we use DNase-seq in combination with analysis of histone modifications to identify multiple classes of epigenetically and functionally distinct cis-regulatory elements (CREs). Through motif analysis and ChIP-seq, we identify several of the crucial TF regulators of NS cells. At the core of the network are TFs of the basic helix-loop-helix (bHLH), nuclear factor I (NFI), SOX, and FOX families, with CREs often densely bound by several of these different TFs. We use machine learning to highlight several crucial regulatory features of the network that underpin NS cell self-renewal and multipotency. We validate our predictions by functional analysis of the bHLH TF OLIG2. This TF makes an important contribution to NS cell self-renewal by concurrently activating pro-proliferation genes and preventing the untimely activation of genes promoting neuronal differentiation and stem cell quiescence.Welcome Trust grants: (WT095908, WT098051), FEBS Long-Term Fellowship, Medical Research Council Grant-in-Aid (U117570528).Cold Spring Harbor Lab PressARCAMateo, Juan Lvan den Berg, Debbie L CHaeussler, MaximilianDrechsel, DanielaGaber, Zachary BCastro, Diogo SRobson, PaulCrawford, Gregory EFlicek, PaulEttwiller, LaurenceWittbrodt, JoachimGuillemot, FrançoisMartynoga, Ben2015-10-21T00:30:09Z2015-012015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.7/415eng10.1101/gr.173435.114info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-11-29T14:34:48Zoai:arca.igc.gulbenkian.pt:10400.7/415Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:11:42.622847Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal |
title |
Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal |
spellingShingle |
Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal Mateo, Juan L Stem Cells OLIG2 |
title_short |
Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal |
title_full |
Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal |
title_fullStr |
Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal |
title_full_unstemmed |
Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal |
title_sort |
Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal |
author |
Mateo, Juan L |
author_facet |
Mateo, Juan L van den Berg, Debbie L C Haeussler, Maximilian Drechsel, Daniela Gaber, Zachary B Castro, Diogo S Robson, Paul Crawford, Gregory E Flicek, Paul Ettwiller, Laurence Wittbrodt, Joachim Guillemot, François Martynoga, Ben |
author_role |
author |
author2 |
van den Berg, Debbie L C Haeussler, Maximilian Drechsel, Daniela Gaber, Zachary B Castro, Diogo S Robson, Paul Crawford, Gregory E Flicek, Paul Ettwiller, Laurence Wittbrodt, Joachim Guillemot, François Martynoga, Ben |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
ARCA |
dc.contributor.author.fl_str_mv |
Mateo, Juan L van den Berg, Debbie L C Haeussler, Maximilian Drechsel, Daniela Gaber, Zachary B Castro, Diogo S Robson, Paul Crawford, Gregory E Flicek, Paul Ettwiller, Laurence Wittbrodt, Joachim Guillemot, François Martynoga, Ben |
dc.subject.por.fl_str_mv |
Stem Cells OLIG2 |
topic |
Stem Cells OLIG2 |
description |
The gene regulatory network (GRN) that supports neural stem cell (NS cell) self-renewal has so far been poorly characterized. Knowledge of the central transcription factors (TFs), the noncoding gene regulatory regions that they bind to, and the genes whose expression they modulate will be crucial in unlocking the full therapeutic potential of these cells. Here, we use DNase-seq in combination with analysis of histone modifications to identify multiple classes of epigenetically and functionally distinct cis-regulatory elements (CREs). Through motif analysis and ChIP-seq, we identify several of the crucial TF regulators of NS cells. At the core of the network are TFs of the basic helix-loop-helix (bHLH), nuclear factor I (NFI), SOX, and FOX families, with CREs often densely bound by several of these different TFs. We use machine learning to highlight several crucial regulatory features of the network that underpin NS cell self-renewal and multipotency. We validate our predictions by functional analysis of the bHLH TF OLIG2. This TF makes an important contribution to NS cell self-renewal by concurrently activating pro-proliferation genes and preventing the untimely activation of genes promoting neuronal differentiation and stem cell quiescence. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-10-21T00:30:09Z 2015-01 2015-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.7/415 |
url |
http://hdl.handle.net/10400.7/415 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1101/gr.173435.114 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Cold Spring Harbor Lab Press |
publisher.none.fl_str_mv |
Cold Spring Harbor Lab Press |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
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1799130572882182144 |