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

Linjia Jiang, Xue Han, Jin Wang, Chen Wang, Xiaoqiang Sun, Jiayi Xie, Guojin Wu, Hiep Phan, Zhenguo Liu, Chengcheng Zhang, Meng Zhao, Xunlei Kang

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1337-1347
Number of pages11
JournalJournal of Experimental Medicine
Volume215
Issue number5
DOIs
StatePublished - May 1 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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