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University of California-San Diego: Dataset Details, ID=GSE81214

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Superfund Research Program

Detection and Models of Toxicant Exposure

Center Director: Robert H. Tukey
Grant Number: P42ES010337
Funding Period: 2000-2023
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Title: RNA-seq of hESC samples upon loss of UPF1.

Accession Number: GSE81214

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE81214

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Array expression profiling by high throughput sequencing

Organism(s): Homo sapiens

Summary: 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 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-b and BMP signaling, which we found NMD acts through to influence definitive endoderm vs. mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages.

Publication(s) associated with this dataset:
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