AI Article Synopsis
- * This study finds that knockout HSCs show reduced quiescence and less self-renewal ability, while normal HSCs are supported by nearby megakaryocytes that produce TGF-β1.
- * The researchers discovered that SHP-1 is crucial for TGF-β signaling in HSCs, as it interacts with TGF-β receptor 1, allowing proper regulation of quiescence, which is absent in knockout HSCs.
Article Abstract
Cell cycle quiescence is critical for hematopoietic stem cell (HSC) maintenance. TGF-β signaling in bone marrow niche has been identified in regulating HSC quiescence; however, the intrinsic regulatory mechanisms remain unclear. This study reports that knockout HSCs have attenuated quiescence and impaired long-term self-renewal. SHP-1-activated HSCs are surrounded by megakaryocytes, which regulate HSC quiescence by producing TGF-β1. Mechanistically, SHP-1 interacts with the immunoreceptor tyrosine-based inhibition motif on TGF-β receptor 1 and is critical for TGF-β signaling activation in HSCs. Functionally, knockout HSCs do not respond to TGF-β-enforced HSC quiescence regulation, both in vitro and in vivo. Therefore, we identify TGF-β-SHP-1 as a novel intrinsic regulatory mechanism for HSC quiescence maintenance.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940262 | PMC |
| http://dx.doi.org/10.1084/jem.20171477 | DOI Listing |
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