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 journalArticle

6 Citations (Scopus)

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

Fingerprint

Hematopoietic Stem Cells
Immunoreceptor Tyrosine-Based Inhibition Motif
Maintenance
Megakaryocytes
Cell Cycle
Bone Marrow

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Jiang, L., Han, X., Wang, J., Wang, C., Sun, X., Xie, J., ... Kang, X. (2018). SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-ß signaling. Journal of Experimental Medicine, 215(5), 1337-1347. https://doi.org/10.1084/jem.20171477

SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-ß signaling. / Jiang, Linjia; Han, Xue; Wang, Jin; Wang, Chen; Sun, Xiaoqiang; Xie, Jiayi; Wu, Guojin; Phan, Hiep; Liu, Zhenguo; Zhang, Chengcheng; Zhao, Meng; Kang, Xunlei.

In: Journal of Experimental Medicine, Vol. 215, No. 5, 01.05.2018, p. 1337-1347.

Research output: Contribution to journalArticle

Jiang, L, Han, X, Wang, J, Wang, C, Sun, X, Xie, J, Wu, G, Phan, H, Liu, Z, Zhang, C, Zhao, M & Kang, X 2018, 'SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-ß signaling', Journal of Experimental Medicine, vol. 215, no. 5, pp. 1337-1347. https://doi.org/10.1084/jem.20171477
Jiang, Linjia ; Han, Xue ; Wang, Jin ; Wang, Chen ; Sun, Xiaoqiang ; Xie, Jiayi ; Wu, Guojin ; Phan, Hiep ; Liu, Zhenguo ; Zhang, Chengcheng ; Zhao, Meng ; Kang, Xunlei. / SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-ß signaling. In: Journal of Experimental Medicine. 2018 ; Vol. 215, No. 5. pp. 1337-1347.
@article{aa901b3311324e9db2d375767bcedc5d,
title = "SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-{\ss} signaling",
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-{\ss}1. 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.",
author = "Linjia Jiang and Xue Han and Jin Wang and Chen Wang and Xiaoqiang Sun and Jiayi Xie and Guojin Wu and Hiep Phan and Zhenguo Liu and Chengcheng Zhang and Meng Zhao and Xunlei Kang",
year = "2018",
month = "5",
day = "1",
doi = "10.1084/jem.20171477",
language = "English (US)",
volume = "215",
pages = "1337--1347",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "5",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=85046831669&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046831669&partnerID=8YFLogxK

U2 - 10.1084/jem.20171477

DO - 10.1084/jem.20171477

M3 - Article

C2 - 29669741

AN - SCOPUS:85046831669

VL - 215

SP - 1337

EP - 1347

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 5

ER -