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Stem Cell Reports. 2016 Jun 14;6(6):844-857. doi: 10.1016/j.stemcr.2016.05.008.

Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate.

Author information

1
Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
2
School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85281, USA.
3
Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: mfwilkinson@ucsd.edu.

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.

PMID:
27304915
PMCID:
PMC4912386
DOI:
10.1016/j.stemcr.2016.05.008
[Indexed for MEDLINE]
Free PMC Article

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