z-logo
open-access-imgOpen Access
Hemgn Protects Hematopoietic Stem and Progenitor Cells Against Transplantation Stress Through Negatively Regulating IFN‐ γ Signaling
Author(s) -
Zhao Ke,
Liu JinFang,
Zhu YaXin,
Dong XiaoMing,
Yin RongHua,
Liu Xian,
Gao HuiYing,
Xiao FengJun,
Gao Rui,
Wang Qi,
Zhan YiQun,
Yu Miao,
Chen Hui,
Ning HongMei,
Zhang CaiBo,
Yang XiaoMing,
Li ChangYan
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202103838
Subject(s) - haematopoiesis , progenitor cell , homing (biology) , transplantation , stem cell , microbiology and biotechnology , biology , cancer research , signal transduction , bone marrow , immunology , medicine , ecology
Hematopoietic stem and progenitor cells (HSPCs) possess the remarkable ability to regenerate the whole blood system in response to ablated stress demands. Delineating the mechanisms that maintain HSPCs during regenerative stresses is increasingly important. Here, it is shown that Hemgn is significantly induced by hematopoietic stresses including irradiation and bone marrow transplantation (BMT). Hemgn deficiency does not disturb steady‐state hematopoiesis in young mice. Hemgn −/‐ HSPCs display defective engraftment activity during BMT with reduced homing and survival and increased apoptosis. Transcriptome profiling analysis reveals that upregulated genes in transplanted Hemgn −/− HSPCs are enriched for gene sets related to interferon gamma (IFN‐ γ ) signaling. Hemgn −/− HSPCs show enhanced responses to IFN‐ γ treatment and increased aging over time. Blocking IFN‐ γ signaling in irradiated recipients either pharmacologically or genetically rescues Hemgn −/‐ HSPCs engraftment defect. Mechanistical studies reveal that Hemgn deficiency sustain nuclear Stat1 tyrosine phosphorylation via suppressing T‐cell protein tyrosine phosphatase TC45 activity. Spermidine, a selective activator of TC45, rescues exacerbated phenotype of HSPCs in IFN‐ γ ‐treated Hemgn −/− mice. Collectively, these results identify that Hemgn is a critical regulator for successful engraftment and reconstitution of HSPCs in mice through negatively regulating IFN‐ γ signaling. Targeted Hemgn may be used to improve conditioning regimens and engraftment during HSPCs transplantation.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here