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

Author

Listed:
  • Hyun Ju Lee

    (University of Cologne)

  • Deniz Bartsch

    (University of Cologne
    Center for Molecular Medicine Cologne (CMMC), University of Cologne)

  • Cally Xiao

    (University of Cologne
    University Hospital of Cologne)

  • Santiago Guerrero

    (Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology
    Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnologica Equinoccial)

  • Gaurav Ahuja

    (University of Cologne
    Center for Molecular Medicine Cologne (CMMC), University of Cologne)

  • Christina Schindler

    (University of Cologne)

  • James J. Moresco

    (10550 North Torrey Pines Road, SR111, The Scripps Research Institute)

  • John R. Yates

    (10550 North Torrey Pines Road, SR111, The Scripps Research Institute)

  • Fátima Gebauer

    (Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology)

  • Hisham Bazzi

    (University of Cologne
    University Hospital of Cologne)

  • Christoph Dieterich

    (Department of Internal Medicine III and Klaus Tschira Institute for Computational Cardiology, Neuenheimer Feld 669, University Hospital)

  • Leo Kurian

    (University of Cologne
    Center for Molecular Medicine Cologne (CMMC), University of Cologne)

  • David Vilchez

    (University of Cologne)

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.

Suggested Citation

  • Hyun Ju Lee & Deniz Bartsch & Cally Xiao & Santiago Guerrero & Gaurav Ahuja & Christina Schindler & James J. Moresco & John R. Yates & Fátima Gebauer & Hisham Bazzi & Christoph Dieterich & Leo Kurian , 2017. "A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells," Nature Communications, Nature, vol. 8(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01744-5
    DOI: 10.1038/s41467-017-01744-5
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    Cited by:

    1. Anna Laddach & Song Hui Chng & Reena Lasrado & Fränze Progatzky & Michael Shapiro & Alek Erickson & Marisol Sampedro Castaneda & Artem V. Artemov & Ana Carina Bon-Frauches & Eleni-Maria Amaniti & Jens, 2023. "A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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