Joint Program in Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
Stem Cells. 2021 Feb;39(2):183-195. doi: 10.1002/stem.3308. Epub 2020 Dec 9.
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.
造血干细胞（HSCs）在稳态下维持静息状态；然而，在应激下，它们被迫增殖和扩增以补充血液系统。应激造血的分子基础仍有待充分理解。在这项研究中，我们报告了干扰素调节因子 7（IRF7）是应激造血的重要调节因子。干扰素调节因子 7（IRF7）对于正常造血是可有可无的，但其缺乏显著增强了造血干细胞和祖细胞（HSPCs）的再生，并改善了应激下 HSCs 的长期重编程。机制研究表明，CXCR4 被鉴定为 IRF7 的下游靶标。过表达 CXCR4 可消除 IRF7 缺陷 HSPCs 在应激下的增殖和再生增强。在人脐带血来源的 HSCs 中也获得了类似的结果。这些观察结果表明，IRF7 在应激下的造血再生中发挥重要作用。
