A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells

While the transcriptional network of human embryonic stem cells (hESCs) has been extensively studied, relatively little is known about how post-transcriptional modulations determine hESC function. RNA-binding proteins play central roles in RNA regulation, including translation and turnover. Here we...

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Autores: Ju Lee, Hyun, Bartsch, Deniz, Xiao, Cally, Guerrero Jijon, Santiago Xavier, Ahuja, Gaurav, Schindler, Christina, Moresco, James J., Yates, John R., Gebauer, Fátima, Bazzi, Hisham, Dieterich, Christoph, Kurian, Leo, Vílchez, David
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/34962
Acceso en línea:http://hdl.handle.net/10230/34962
http://dx.doi.org/10.1038/s41467-017-01744-5
Access Level:acceso abierto
Palabra clave:Developmental neurogenesis
Differentiation
Embryonic stem cells
Pluripotency
Rna decay
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spelling A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cellsJu Lee, HyunBartsch, DenizXiao, CallyGuerrero Jijon, Santiago XavierAhuja, GauravSchindler, ChristinaMoresco, James J.Yates, John R.Gebauer, FátimaBazzi, HishamDieterich, ChristophKurian, LeoVílchez, DavidDevelopmental neurogenesisDifferentiationEmbryonic stem cellsPluripotencyRna decayWhile the transcriptional network of human embryonic stem cells (hESCs) has been extensively studied, relatively little is known about how post-transcriptional modulations determine hESC function. RNA-binding proteins play central roles in RNA regulation, including translation and turnover. Here we show that the RNA-binding protein CSDE1 (cold shock domain containing E1) is highly expressed in hESCs to maintain their undifferentiated state and prevent default neural fate. Notably, loss of CSDE1 accelerates neural differentiation and potentiates neurogenesis. Conversely, ectopic expression of CSDE1 impairs neural differentiation. We find that CSDE1 post-transcriptionally modulates core components of multiple regulatory nodes of hESC identity, neuroectoderm commitment and neurogenesis. Among these key pro-neural/neuronal factors, CSDE1 binds fatty acid binding protein 7 (FABP7) and vimentin (VIM) mRNAs, as well as transcripts involved in neuron projection development regulating their stability and translation. Thus, our results uncover CSDE1 as a central post-transcriptional regulator of hESC identity and neurogenesis.The Deutsche Forschungsgemeinschaft (DFG) (CECAD) and the European Research Council (ERC Starting Grant-677427 StemProteostasis) supported this research. J.J.M. and J.R.Y. were supported by the National Center for Research Resources (5P41RR011823). We thank I.S. for advice on CRISPR/Cas9 method, M.R. for analysis of enriched GO terms in interactome experiments and S.L. for her technical support.Nature Publishing Group201820182017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/34962http://dx.doi.org/10.1038/s41467-017-01744-5reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNat Commun. 2017 Nov 13;8(1):1456info:eu-repo/grantAgreement/EC/H2020/677427© The Author(s) 2017. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/349622026-06-12T07:21:37Z
dc.title.none.fl_str_mv A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells
title A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells
spellingShingle A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells
Ju Lee, Hyun
Developmental neurogenesis
Differentiation
Embryonic stem cells
Pluripotency
Rna decay
title_short A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells
title_full A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells
title_fullStr A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells
title_full_unstemmed A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells
title_sort A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells
dc.creator.none.fl_str_mv Ju Lee, Hyun
Bartsch, Deniz
Xiao, Cally
Guerrero Jijon, Santiago Xavier
Ahuja, Gaurav
Schindler, Christina
Moresco, James J.
Yates, John R.
Gebauer, Fátima
Bazzi, Hisham
Dieterich, Christoph
Kurian, Leo
Vílchez, David
author Ju Lee, Hyun
author_facet Ju Lee, Hyun
Bartsch, Deniz
Xiao, Cally
Guerrero Jijon, Santiago Xavier
Ahuja, Gaurav
Schindler, Christina
Moresco, James J.
Yates, John R.
Gebauer, Fátima
Bazzi, Hisham
Dieterich, Christoph
Kurian, Leo
Vílchez, David
author_role author
author2 Bartsch, Deniz
Xiao, Cally
Guerrero Jijon, Santiago Xavier
Ahuja, Gaurav
Schindler, Christina
Moresco, James J.
Yates, John R.
Gebauer, Fátima
Bazzi, Hisham
Dieterich, Christoph
Kurian, Leo
Vílchez, David
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Developmental neurogenesis
Differentiation
Embryonic stem cells
Pluripotency
Rna decay
topic Developmental neurogenesis
Differentiation
Embryonic stem cells
Pluripotency
Rna decay
description While the transcriptional network of human embryonic stem cells (hESCs) has been extensively studied, relatively little is known about how post-transcriptional modulations determine hESC function. RNA-binding proteins play central roles in RNA regulation, including translation and turnover. Here we show that the RNA-binding protein CSDE1 (cold shock domain containing E1) is highly expressed in hESCs to maintain their undifferentiated state and prevent default neural fate. Notably, loss of CSDE1 accelerates neural differentiation and potentiates neurogenesis. Conversely, ectopic expression of CSDE1 impairs neural differentiation. We find that CSDE1 post-transcriptionally modulates core components of multiple regulatory nodes of hESC identity, neuroectoderm commitment and neurogenesis. Among these key pro-neural/neuronal factors, CSDE1 binds fatty acid binding protein 7 (FABP7) and vimentin (VIM) mRNAs, as well as transcripts involved in neuron projection development regulating their stability and translation. Thus, our results uncover CSDE1 as a central post-transcriptional regulator of hESC identity and neurogenesis.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/34962
http://dx.doi.org/10.1038/s41467-017-01744-5
url http://hdl.handle.net/10230/34962
http://dx.doi.org/10.1038/s41467-017-01744-5
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nat Commun. 2017 Nov 13;8(1):1456
info:eu-repo/grantAgreement/EC/H2020/677427
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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