Nonsense-mediated RNA decay influences human embryonic stem cell fate

Chih Hong Lou, Jennifer Dumdie, Alexandra Goetz, Eleen Y. Shum, David Brafman, Xiaoyan Liao, Sergio Mora-Castilla, Madhuvanthi Ramaiah, Heidi Cook-Andersen, Louise Laurent, Miles F. Wilkinson

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages.

Original languageEnglish (US)
Pages (from-to)844-857
Number of pages14
JournalStem Cell Reports
Volume6
Issue number6
DOIs
StatePublished - Jun 14 2016

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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