TY - JOUR
T1 - SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-ß signaling
AU - Jiang, Linjia
AU - Han, Xue
AU - Wang, Jin
AU - Wang, Chen
AU - Sun, Xiaoqiang
AU - Xie, Jiayi
AU - Wu, Guojin
AU - Phan, Hiep
AU - Liu, Zhenguo
AU - Zhang, Chengcheng
AU - Zhao, Meng
AU - Kang, Xunlei
N1 - Publisher Copyright:
© 2018 Jiang et al.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Cell cycle quiescence is critical for hematopoietic stem cell (HSC) maintenance. TGF-ß 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-ß1. Mechanistically, SHP-1 interacts with the immunoreceptor tyrosine-based inhibition motif on TGF-ß receptor 1 and is critical for TGF-ß signaling activation in HSCs. Functionally, Shp-1 knockout HSCs do not respond to TGF-ß-enforced HSC quiescence regulation, both in vitro and in vivo. Therefore, we identify TGF-ß-SHP-1 as a novel intrinsic regulatory mechanism for HSC quiescence maintenance.
AB - Cell cycle quiescence is critical for hematopoietic stem cell (HSC) maintenance. TGF-ß 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-ß1. Mechanistically, SHP-1 interacts with the immunoreceptor tyrosine-based inhibition motif on TGF-ß receptor 1 and is critical for TGF-ß signaling activation in HSCs. Functionally, Shp-1 knockout HSCs do not respond to TGF-ß-enforced HSC quiescence regulation, both in vitro and in vivo. Therefore, we identify TGF-ß-SHP-1 as a novel intrinsic regulatory mechanism for HSC quiescence maintenance.
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U2 - 10.1084/jem.20171477
DO - 10.1084/jem.20171477
M3 - Article
C2 - 29669741
AN - SCOPUS:85046831669
SN - 0022-1007
VL - 215
SP - 1337
EP - 1347
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -