Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate
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 pluripote...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-06-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671116300637 |
| _version_ | 1818513156531552256 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chih-Hong Lou |
| collection | DOAJ |
| description | 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 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. : In this report, Wilkinson and colleagues show that the conserved RNA degradation pathway—nonsense-mediated RNA decay (NMD)—is highly active in human embryonic stem cells (hESCs). They demonstrate that NMD degrades mRNAs encoding components of signaling pathways critical for primary germ-layer differentiation. hESC differentiation modulates NMD magnitude, which strongly influences mesoderm versus definitive endoderm cell fate. |
| first_indexed | 2024-12-10T23:57:16Z |
| format | Article |
| id | doaj.art-98086608a1714f32a8e3dc874d165deb |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-10T23:57:16Z |
| publishDate | 2016-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-98086608a1714f32a8e3dc874d165deb2022-12-22T01:28:33ZengElsevierStem Cell Reports2213-67112016-06-0166844857Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell FateChih-Hong Lou0Jennifer Dumdie1Alexandra Goetz2Eleen Y. Shum3David Brafman4Xiaoyan Liao5Sergio Mora-Castilla6Madhuvanthi Ramaiah7Heidi Cook-Andersen8Louise Laurent9Miles F. Wilkinson10Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USASchool of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85281, USADepartment of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADepartment 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; Corresponding authorSummary: 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. : In this report, Wilkinson and colleagues show that the conserved RNA degradation pathway—nonsense-mediated RNA decay (NMD)—is highly active in human embryonic stem cells (hESCs). They demonstrate that NMD degrades mRNAs encoding components of signaling pathways critical for primary germ-layer differentiation. hESC differentiation modulates NMD magnitude, which strongly influences mesoderm versus definitive endoderm cell fate.http://www.sciencedirect.com/science/article/pii/S2213671116300637 |
| spellingShingle | 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 Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate Stem Cell Reports |
| title | Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate |
| title_full | Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate |
| title_fullStr | Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate |
| title_full_unstemmed | Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate |
| title_short | Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate |
| title_sort | nonsense mediated rna decay influences human embryonic stem cell fate |
| url | http://www.sciencedirect.com/science/article/pii/S2213671116300637 |
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