IRF7 suppresses hematopoietic regeneration under stress via CXCR4,STEM CELLS

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IRF7 suppresses hematopoietic regeneration under stress via CXCR4
STEM CELLS ( IF 4.0 ) Pub Date : 2020-11-30 , DOI: 10.1002/stem.3308
Ying-Ying Chen _{1,

2,

3} , Yu-Feng Liu ₃ , Yong-Dong Liu ₄ , Xiao-Hui Deng _{2,

3} , Jie Zhou _{1,

2,

3}

Affiliation

Hematopoietic stem cells (HSCs) maintain quiescence under steady state; however, they are compelled to proliferate and expand to replenish the blood system under stress. The molecular basis underlying stress hematopoiesis remains to be fully understood. In this study, we reported that IRF7 represents an important regulator of stress hematopoiesis. Interferon regulatory factor 7 (IRF7) was dispensable for normal hematopoiesis, whereas its deficiency significantly enhanced hematopoietic stem and progenitor cells (HSPCs) regeneration and improved long‐term repopulation of HSCs under stress. Mechanistic studies showed that CXCR4 was identified as a downstream target of IRF7. Overexpression of CXCR4 abrogated the enhanced proliferation and regeneration of IRF7‐deficient HSPCs under stress. Similar results were obtained in HSCs from human umbilical cord blood. These observations demonstrated that IRF7 plays an important role in hematopoietic regeneration under stress.

中文翻译：

IRF7通过CXCR4抑制压力下的造血再生

造血干细胞 (HSC) 在稳定状态下保持静止；然而，它们在压力下被迫增殖和扩张以补充血液系统。应激造血的分子基础仍有待充分了解。在这项研究中，我们报道了 IRF7 是应激造血的重要调节因子。干扰素调节因子 7（IRF7）对于正常的造血功能是不必要的，而它的缺乏显着增强了造血干细胞和祖细胞（HSPC）的再生，并改善了压力下 HSC 的长期再增殖。机理研究表明，CXCR4被确定为 IRF7 的下游目标。CXCR4 的过表达消除了压力下 IRF7 缺陷型 HSPC 的增殖和再生增强。在来自人脐带血的 HSC 中获得了类似的结果。这些观察结果表明 IRF7 在压力下的造血再生中起着重要作用。

更新日期：2021-01-28

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