SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-β signaling

Linjia Jiang, Xue Han, Jin Wang, Chen Wang, Xiaoqiang Sun, Jiayi Xie, Guojin Wu, Hiep Phan, Zhenguo Liu, Edward T.H. Yeh, ChengCheng Zhang, Meng Zhao (+1 others)
2018 Journal of Experimental Medicine  
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 thatShp-1knockout 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
more » ... rosine-based inhibition motif on TGF-β receptor 1 and is critical for TGF-β signaling activation in HSCs. Functionally,Shp-1knockout 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.
doi:10.1084/jem.20171477 pmid:29669741 fatcat:2lnzl545dfgkjl6q73nndqdije