Lee, Hyun Ju, Bartsch, Deniz, Xiao, Cally ORCID: 0000-0001-7172-3175, Guerrero, Santiago ORCID: 0000-0003-3473-7214, Ahuja, Gaurav ORCID: 0000-0002-2837-9361, Schindler, Christina, Moresco, James J., Yates, John R., III, Gebauer, Fatima ORCID: 0000-0001-7563-0013, Bazzi, Hisham ORCID: 0000-0001-8388-4005, Dieterich, Christoph, Kurian, Leo ORCID: 0000-0001-7466-5169 and Vilchez, David ORCID: 0000-0002-0801-0743 (2017). A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells. Nat. Commun., 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lee, Hyun JuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartsch, DenizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xiao, CallyUNSPECIFIEDorcid.org/0000-0001-7172-3175UNSPECIFIED
Guerrero, SantiagoUNSPECIFIEDorcid.org/0000-0003-3473-7214UNSPECIFIED
Ahuja, GauravUNSPECIFIEDorcid.org/0000-0002-2837-9361UNSPECIFIED
Schindler, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moresco, James J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yates, John R., IIIUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gebauer, FatimaUNSPECIFIEDorcid.org/0000-0001-7563-0013UNSPECIFIED
Bazzi, HishamUNSPECIFIEDorcid.org/0000-0001-8388-4005UNSPECIFIED
Dieterich, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurian, LeoUNSPECIFIEDorcid.org/0000-0001-7466-5169UNSPECIFIED
Vilchez, DavidUNSPECIFIEDorcid.org/0000-0002-0801-0743UNSPECIFIED
URN: urn:nbn:de:hbz:38-211301
DOI: 10.1038/s41467-017-01744-5
Journal or Publication Title: Nat. Commun.
Volume: 8
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
RNA-BINDING PROTEIN; COLD-SHOCK DOMAINS; MESSENGER-RNA; N-RAS; IN-VITRO; TRANSLATIONAL REPRESSION; PRIMED PLURIPOTENCY; DOSAGE COMPENSATION; UNR TRANSLATION; NERVOUS-SYSTEMMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21130

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