A hierarchical network controls protein translation during murine embryonic stem cell self-renewal and differentiation
Open accessAbstract
Stem cell differentiation involves changes in transcription, but little is known about translational control during differentiation. We comprehensively profiled gene expression during differentiation of murine embryonic stem cells (ESCs) into embryoid bodies by integrating transcriptome analysis with global assessment of ribosome loading. While protein synthesis was parsimonious during self-renewal, differentiation induced an anabolic switch, with global increases in transcript abundance, polysome content, protein synthesis, and protein content. Furthermore, 78% of transcripts showed increased ribosome loading, thereby enhancing translational efficiency. Transcripts under exclusive translational control included the transcription factor ATF5, the tumor suppressor DCC, and the beta-catenin agonist Wnt1. We show that a hierarchy of translational regulators, including mTOR, 4EBP1, and the RNA-binding proteins DAZL and GRSF1, control global and selective protein synthesis during ESC differentiation. Parsimonious translation in pluripotent state and hierarchical translational regulation during differentiation may be important quality controls for self-renewal and choice of fate in ESCs.
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Prior polysome profiling work indicated a global rise in cellular translation during early embryonic stem cell differentiation.
“Polysome profiling experiments have suggested a global increase in cellular translation during early ES cell differentiation, and we see a modest upregulation of RPs in our early timepoint (Sampath et al., 2008).”
From Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes (2011) · cites this paper as Sampath et al., 2008
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References 56 · Cited by 277
Research works printed but not linked: 1
- Cell Stem Cell Translational Control during ESC Differentiation Cell Stem Cell 2, 448-460, May 2008 ª2008 Elsevier Inc. 459
- Authors
- Sampath, P., Pritchard, D. K., Pabon, L., Reinecke, H., Schwartz, S. M., Morris, D. R., & Murry, C. E.
- Affiliations
- University of Washington (US)
- Corresponding author
- Morris, David R.
- Murry, Charles E.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 2
- Issue
- 5
- Pages
- 448-460
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2084521437
- Cited by
- 277
- References
- 56
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 14 · 2023: 16 · 2022: 17 · 2021: 15 · 2020: 18 · 2019: 13 · 2018: 13 · 2017: 13 · 2016: 14 · 2015: 21 · 2014: 19 · 2013: 19 · 2012: 14
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington
- Johns Hopkins University
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL072370, R01HL072370, HL-64387, HL84642, R01HL061553, HL61553, HL3171, R01HL084642)
- National Cancer Institute (R33CA089807, CA89807)
- National Institute of General Medical Sciences (P20GM069983, GM-69983)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- translational regulation, embryonic stem cell differentiation, embryoid bodies, ribosome loading, polysome profiling, protein synthesis, mTOR, 4E-BP1, DAZL, GRSF1, ATF5, DCC, Wnt1, β-catenin, pluripotency, self-renewal, RNA-binding proteins
- MeSH terms
- Animals, Carrier Proteins, Cell Differentiation, Phosphoproteins, Transcription, Genetic, Signal Transduction, RNA-Binding Proteins, Cell Cycle Proteins, Gene Expression Profiling, Eukaryotic Initiation Factors, Pluripotent Stem Cells, Protein Modification, Translational, Adaptor Proteins, Signal Transducing, Cell Proliferation, Wnt1 Protein, beta Catenin, Mice, Activating Transcription Factors, Embryonic Stem Cells
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