Acute Loss of Cited2 Impairs Nanog Expression and Decreases Self-Renewal of Mouse Embryonic Stem Cells
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/10400.1/11640 |
Resumo: | Identifying novel players of the pluripotency gene regulatory network centered on Oct4, Sox2, and Nanog as well as delineating the interactions within the complex network is key to understanding self-renewal and early cell fate commitment of embryonic stem cells (ESC). While overexpression of the transcriptional regulator Cited2 sustains ESC pluripotency, its role in ESC functions remains unclear. Here, we show that Cited2 is important for proliferation, survival, and self-renewal of mouse ESC. We position Cited2 within the pluripotency gene regulatory network by defining Nanog, Tbx3, and Klf4 as its direct targets. We also demonstrate that the defects caused by Cited2 depletion are, at least in part, rescued by Nanog constitutive expression. Finally, we demonstrate that Cited2 is required for and enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. |
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Acute Loss of Cited2 Impairs Nanog Expression and Decreases Self-Renewal of Mouse Embryonic Stem CellsTranscriptional NetworkSignaling PathwaysHeart DevelopmentGround-StatePluripotencyCoactivatorGeneHeterogeneityHif-1-AlphaDeficiencyIdentifying novel players of the pluripotency gene regulatory network centered on Oct4, Sox2, and Nanog as well as delineating the interactions within the complex network is key to understanding self-renewal and early cell fate commitment of embryonic stem cells (ESC). While overexpression of the transcriptional regulator Cited2 sustains ESC pluripotency, its role in ESC functions remains unclear. Here, we show that Cited2 is important for proliferation, survival, and self-renewal of mouse ESC. We position Cited2 within the pluripotency gene regulatory network by defining Nanog, Tbx3, and Klf4 as its direct targets. We also demonstrate that the defects caused by Cited2 depletion are, at least in part, rescued by Nanog constitutive expression. Finally, we demonstrate that Cited2 is required for and enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells.National Portuguese through FCT-Fundacao para a Ciencia e a Tecnologia [PEst-OE/EQB/LA0023/2013, PTDC/SAU-ENB/111702/2009]; Camara Municipal de Oeiras; Merck Sharp & Dhome Foundation-Portugal; CRUK; Leukaemia & Lymphoma Research; Kay Kendall Leukaemia Fund; Wellcome Trust; Medical Research Council; Cancer Research UK [12796, 14633]; Great Ormond Street Hospital Childrens Charity [W1062]; Medical Research Council [MC_U137973817, G1000801g, MC_qA137913]WileySapientiaKranc, Kamil R.Oliveira, DanielArmesilla-Diaz, AlejandroPacheco-Leyva, IvetteMatias, Ana CatarinaEscapa, Ana LuísaSubramani, ChithraWheadon, HelenTrindade, MarleneNichols, JenniferKaji, KeisukeEnver, TariqBragança, José2018-12-07T14:53:41Z2015-032015-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/11640eng1066-509910.1002/stem.1889info: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:RCAAP2023-07-24T10:23:29Zoai:sapientia.ualg.pt:10400.1/11640Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:03:07.215491Repositório 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 |
Acute Loss of Cited2 Impairs Nanog Expression and Decreases Self-Renewal of Mouse Embryonic Stem Cells |
title |
Acute Loss of Cited2 Impairs Nanog Expression and Decreases Self-Renewal of Mouse Embryonic Stem Cells |
spellingShingle |
Acute Loss of Cited2 Impairs Nanog Expression and Decreases Self-Renewal of Mouse Embryonic Stem Cells Kranc, Kamil R. Transcriptional Network Signaling Pathways Heart Development Ground-State Pluripotency Coactivator Gene Heterogeneity Hif-1-Alpha Deficiency |
title_short |
Acute Loss of Cited2 Impairs Nanog Expression and Decreases Self-Renewal of Mouse Embryonic Stem Cells |
title_full |
Acute Loss of Cited2 Impairs Nanog Expression and Decreases Self-Renewal of Mouse Embryonic Stem Cells |
title_fullStr |
Acute Loss of Cited2 Impairs Nanog Expression and Decreases Self-Renewal of Mouse Embryonic Stem Cells |
title_full_unstemmed |
Acute Loss of Cited2 Impairs Nanog Expression and Decreases Self-Renewal of Mouse Embryonic Stem Cells |
title_sort |
Acute Loss of Cited2 Impairs Nanog Expression and Decreases Self-Renewal of Mouse Embryonic Stem Cells |
author |
Kranc, Kamil R. |
author_facet |
Kranc, Kamil R. Oliveira, Daniel Armesilla-Diaz, Alejandro Pacheco-Leyva, Ivette Matias, Ana Catarina Escapa, Ana Luísa Subramani, Chithra Wheadon, Helen Trindade, Marlene Nichols, Jennifer Kaji, Keisuke Enver, Tariq Bragança, José |
author_role |
author |
author2 |
Oliveira, Daniel Armesilla-Diaz, Alejandro Pacheco-Leyva, Ivette Matias, Ana Catarina Escapa, Ana Luísa Subramani, Chithra Wheadon, Helen Trindade, Marlene Nichols, Jennifer Kaji, Keisuke Enver, Tariq Bragança, José |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Kranc, Kamil R. Oliveira, Daniel Armesilla-Diaz, Alejandro Pacheco-Leyva, Ivette Matias, Ana Catarina Escapa, Ana Luísa Subramani, Chithra Wheadon, Helen Trindade, Marlene Nichols, Jennifer Kaji, Keisuke Enver, Tariq Bragança, José |
dc.subject.por.fl_str_mv |
Transcriptional Network Signaling Pathways Heart Development Ground-State Pluripotency Coactivator Gene Heterogeneity Hif-1-Alpha Deficiency |
topic |
Transcriptional Network Signaling Pathways Heart Development Ground-State Pluripotency Coactivator Gene Heterogeneity Hif-1-Alpha Deficiency |
description |
Identifying novel players of the pluripotency gene regulatory network centered on Oct4, Sox2, and Nanog as well as delineating the interactions within the complex network is key to understanding self-renewal and early cell fate commitment of embryonic stem cells (ESC). While overexpression of the transcriptional regulator Cited2 sustains ESC pluripotency, its role in ESC functions remains unclear. Here, we show that Cited2 is important for proliferation, survival, and self-renewal of mouse ESC. We position Cited2 within the pluripotency gene regulatory network by defining Nanog, Tbx3, and Klf4 as its direct targets. We also demonstrate that the defects caused by Cited2 depletion are, at least in part, rescued by Nanog constitutive expression. Finally, we demonstrate that Cited2 is required for and enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-03 2015-03-01T00:00:00Z 2018-12-07T14:53:41Z |
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/10400.1/11640 |
url |
http://hdl.handle.net/10400.1/11640 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1066-5099 10.1002/stem.1889 |
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 |
Wiley |
publisher.none.fl_str_mv |
Wiley |
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 |
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