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Published on: October 27, 2020
SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-β signaling
Linjia Jiang1, Xue Han1,2, Jin Wang1,3,2,4
1RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
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 Shp-1 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, Shp-1 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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