AI Article Synopsis
- HSC differentiation is influenced by both internal (cell-intrinsic) and external (cell-extrinsic) factors, with a focus on how post-translational mechanisms might impact this process.
- The research highlights the role of the c-Myc protein's stability, regulated by the ubiquitin ligase Fbw7, in determining HSC quiescence and its associated gene expression.
- Distinct responses to c-Myc-regulated gene expression were observed between adult HSCs and embryonic stem cells, indicating a complex interaction involving specific regulators that dictate HSC differentiation.
Article Abstract
Hematopoietic stem cell (HSC) differentiation is regulated by cell-intrinsic and cell-extrinsic cues. In addition to transcriptional regulation, post-translational regulation may also control HSC differentiation. To test this hypothesis, we visualized the ubiquitin-regulated protein stability of a single transcription factor, c-Myc. The stability of c-Myc protein was indicative of HSC quiescence, and c-Myc protein abundance was controlled by the ubiquitin ligase Fbw7. Fine changes in the stability of c-Myc protein regulated the HSC gene-expression signature. Using whole-genome genomic approaches, we identified specific regulators of HSC function directly controlled by c-Myc binding; however, adult HSCs and embryonic stem cells sensed and interpreted c-Myc-regulated gene expression in distinct ways. Our studies show that a ubiquitin ligase-substrate pair can orchestrate the molecular program of HSC differentiation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825759 | PMC |
| http://dx.doi.org/10.1038/ni.1839 | DOI Listing |
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