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

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dc.contributor.author Ju Lee, Hyun
dc.contributor.author Bartsch, Deniz
dc.contributor.author Xiao, Cally
dc.contributor.author Guerrero Jijon, Santiago Xavier
dc.contributor.author Ahuja, Gaurav
dc.contributor.author Schindler, Christina
dc.contributor.author Moresco, James J.
dc.contributor.author Yates, John R.
dc.contributor.author Gebauer, Fátima
dc.contributor.author Bazzi, Hisham
dc.contributor.author Dieterich, Christoph
dc.contributor.author Kurian, Leo
dc.contributor.author Vílchez, David
dc.date.accessioned 2018-06-25T11:25:25Z
dc.date.available 2018-06-25T11:25:25Z
dc.date.issued 2017
dc.identifier.citation Ju Lee H, Bartsch D, Xiao C, Guerrero S, Ahuja G, Schindler C et al. A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells. Nat Commun. 2017 Nov 13;8(1):1456. DOI: 10.1038/s41467-017-01744-5
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/34962
dc.description.abstract 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.
dc.description.sponsorship 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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Publishing Group
dc.relation.ispartof Nat Commun. 2017 Nov 13;8(1):1456
dc.rights © 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/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41467-017-01744-5
dc.subject.keyword Developmental neurogenesis
dc.subject.keyword Differentiation
dc.subject.keyword Embryonic stem cells
dc.subject.keyword Pluripotency
dc.subject.keyword Rna decay
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/677427
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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