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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fatty Acid-Binding Protein 7 / genetics
  • Fatty Acid-Binding Protein 7 / metabolism*
  • Gene Expression Regulation / genetics
  • Human Embryonic Stem Cells / cytology*
  • Humans
  • Mice
  • Nervous System / embryology
  • Neural Plate / cytology
  • Neural Plate / embryology*
  • Neural Stem Cells / cytology
  • Neurogenesis / genetics*
  • Neurogenesis / physiology
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Vimentin / genetics
  • Vimentin / metabolism*


  • CSDE1 protein, human
  • DNA-Binding Proteins
  • FABP7 protein, human
  • Fatty Acid-Binding Protein 7
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Tumor Suppressor Proteins
  • Vim protein, mouse
  • Vimentin