TY - JOUR
T1 - Nonsense-mediated RNA decay influences human embryonic stem cell fate
AU - Lou, Chih Hong
AU - Dumdie, Jennifer
AU - Goetz, Alexandra
AU - Shum, Eleen Y.
AU - Brafman, David
AU - Liao, Xiaoyan
AU - Mora-Castilla, Sergio
AU - Ramaiah, Madhuvanthi
AU - Cook-Andersen, Heidi
AU - Laurent, Louise
AU - Wilkinson, Miles F.
N1 - Publisher Copyright:
© 2016 The Authors.
PY - 2016/6/14
Y1 - 2016/6/14
N2 - 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.
AB - 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.
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U2 - 10.1016/j.stemcr.2016.05.008
DO - 10.1016/j.stemcr.2016.05.008
M3 - Article
C2 - 27304915
AN - SCOPUS:84975318358
SN - 2213-6711
VL - 6
SP - 844
EP - 857
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 6
ER -