Proteomics

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


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 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Embryo, Stem Cell

SUBMITTER: David Vilchez  

LAB HEAD: David Vilchez

PROVIDER: PXD007270 | Pride | 2018-05-16

REPOSITORIES: Pride

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Publications

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

Ju Lee Hyun H   Bartsch Deniz D   Xiao Cally C   Guerrero Santiago S   Ahuja Gaurav G   Schindler Christina C   Moresco James J JJ   Yates John R JR   Gebauer Fátima F   Bazzi Hisham H   Dieterich Christoph C   Kurian Leo L   Vilchez David D  

Nature communications 20171113 1


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  ...[more]

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