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, Hyunca
  • dc.contributor.author Bartsch, Denizca
  • dc.contributor.author Xiao, Callyca
  • dc.contributor.author Guerrero Jijon, Santiago Xavierca
  • dc.contributor.author Ahuja, Gauravca
  • dc.contributor.author Schindler, Christinaca
  • dc.contributor.author Moresco, James J.ca
  • dc.contributor.author Yates, John R.ca
  • dc.contributor.author Gebauer, Fátimaca
  • dc.contributor.author Bazzi, Hishamca
  • dc.contributor.author Dieterich, Christophca
  • dc.contributor.author Kurian, Leoca
  • dc.contributor.author Vílchez, Davidca
  • dc.date.accessioned 2018-06-25T11:25:25Z
  • dc.date.available 2018-06-25T11:25:25Z
  • dc.date.issued 2017
  • 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.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.doi http://dx.doi.org/10.1038/s41467-017-01744-5
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/34962
  • dc.language.iso eng
  • dc.publisher Nature Publishing Groupca
  • dc.relation.ispartof Nat Commun. 2017 Nov 13;8(1):1456
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/677427
  • 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.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • 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.title A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cellsca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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