Format

Send to

Choose Destination
J Exp Med. 2018 May 7;215(5):1337-1347. doi: 10.1084/jem.20171477. Epub 2018 Apr 18.

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

Jiang L1, Han X1,2, Wang J1,3,2,4, Wang C3,2, Sun X2, Xie J1,2, Wu G5, Phan H5, Liu Z3, Yeh ETH, Zhang C6, Zhao M7,2,8, Kang X9.

Author information

1
RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
2
Key Laboratory of Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-Sen University, Ministry of Education, Guangzhou, China.
3
Center for Precision Medicine, Department of Medicine, University of Missouri, Columbia, MO.
4
Department of Hematology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
5
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX.
6
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX Alec.Zhang@UTSouthwestern.edu.
7
RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China zhaom38@mail.sysu.edu.cn.
8
Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
9
Center for Precision Medicine, Department of Medicine, University of Missouri, Columbia, MO kangxu@health.missouri.edu.

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.

PMID:
29669741
PMCID:
PMC5940262
DOI:
10.1084/jem.20171477
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center