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Nat Commun. 2017 Nov 13;8(1):1456. doi: 10.1038/s41467-017-01744-5.

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

Author information

1
Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph Stelzmann Strasse 26, 50931, Cologne, Germany.
2
Laboratory for Developmental and Regenerative RNA biology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Str. 21, 50931, Cologne, Germany.
3
Department of Dermatology and Venereology, University Hospital of Cologne, Joseph Stelzmann Strasse 26, 50931, Cologne, Germany.
4
Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003, Barcelona, Spain.
5
Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnologica Equinoccial, Avenue Mariscal Sucre, 170129, Quito, Ecuador.
6
Department of Chemical Physiology, 10550 North Torrey Pines Road, SR111, The Scripps Research Institute, La Jolla, CA, 92037, USA.
7
Section of Bioinformatics and Systems Cardiology, Department of Internal Medicine III and Klaus Tschira Institute for Computational Cardiology, Neuenheimer Feld 669, University Hospital, 69120, Heidelberg, Germany.
8
Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph Stelzmann Strasse 26, 50931, Cologne, Germany. dvilchez@uni-koeln.de.

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.

PMID:
29129916
PMCID:
PMC5682285
DOI:
10.1038/s41467-017-01744-5
[Indexed for MEDLINE]
Free PMC Article

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