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

Autor: Gaurav Ahuja, John R. Yates, Fátima Gebauer, Deniz Bartsch, Christoph Dieterich, Santiago Guerrero, Leo Kurian, Christina Schindler, Hisham Bazzi, David Vilchez, Hyun Ju Lee, Cally Xiao, James J. Moresco
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Pluripotency
Embryonic stem cells
Neurogenesis
Science
Human Embryonic Stem Cells
General Physics and Astronomy
Developmental neurogenesis
Biology
Nervous System
Article
General Biochemistry
Genetics and Molecular Biology
Cell Line
Mice
03 medical and health sciences
Neural Stem Cells
Animals
Humans
Vimentin
RNA
Messenger
RNA
Small Interfering
lcsh:Science
reproductive and urinary physiology
Rna decay
Regulation of gene expression
Neural Plate
Multidisciplinary
Neuroectoderm
Tumor Suppressor Proteins
Neuron projection
RNA-Binding Proteins
General Chemistry
equipment and supplies
Embryonic stem cell
Neural stem cell
Cell biology
DNA-Binding Proteins
030104 developmental biology
Gene Expression Regulation
Differentiation
embryonic structures
RNA Interference
Ectopic expression
lcsh:Q
biological phenomena
cell phenomena
and immunity
Fatty Acid-Binding Protein 7
Neural plate
Zdroj: Nature Communications, Vol 8, Iss 1, Pp 1-19 (2017)
Nature Communications
Popis: 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.
Unlike transcriptional regulation of hESC identity, little is known post-transcriptionally. Here, the authors show that the RNA binding protein CSDE1 regulates core components of hESC identity, neurectoderm commitment and neurogenesis to maintain pluripotency and prevent neural differentiation.
Databáze: OpenAIRE
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