Details

Autor(en) / Beteiligte

• Jiang, Linjia
• Han, Xue
• Wang, Jin
• Wang, Chen
• Sun, Xiaoqiang
• Xie, Jiayi
• Wu, Guojin
• Phan, Hiep
• Liu, Zhenguo
• Yeh, Edward T H
• Zhang, ChengCheng
• Zhao, Meng
• Kang, Xunlei

Titel

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

Ist Teil von

• The Journal of experimental medicine, 2018-05, Vol.215 (5), p.1337-1347

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• 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.