SHP-1 Regulates Hematopoietic Stem Cell Quiescence by Coordinating TGF-β Signaling

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2018 Apr 20

PMID 29669741

Citations 30

Authors

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

Xunlei Kang

Affiliations

Soon will be listed here.

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.

Citing Articles

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