Programmed cell death regulates hematopoietic cell homeostasis under radiation conditions

作者：Manling Shu, Jinfu Zhang, Yuhong Peng, Zhengyang Li, Xin Shu, Jie Wang, Huihong Zeng, Lijian Shao · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04502-3 · 被引用次数：5 · 研究领域：Effects of Radiation Exposure、Immune Response and Inflammation、Cell death mechanisms and regulation

It is well-known that hematopoietic cells are sensitive to irradiation exposure. Apoptosis, necroptosis, pyroptosis and ferroptosis might contribute to irradiation-induced hematopoietic injury. However, it is uncertain whether different hematopoietic cells apply specific cell death pathways under irradiation exposure. We investigated the role of different programmed cell death pathways in irradiation-induced hematopoietic cell injury. In order to study the acute and long-term effects of ionizing radiation on hematopoietic system, we established injury models of mice at different time points after irradiation and measured the proportion of hematopoietic stem progenitor cells by flow cytometry. The pattern of programmed cell death involved in radiation-induced hematopoietic cell injury was identified through the analysis of different populations of hematopoietic cells in the bone marrow by immunomagnetic bead sorting combined with qRT-PCR and flow cytometry. The role of pyroptosis in radiation injury of hematopoietic stem cells was further studied by Caspase-1 inhibitor VX-765 application. In vivo spleen colony formation, competitive bone marrow transplantation and secondary transplantation were used to verify the protective effect of inhibiting Caspase-1 on hematopoietic stem cells damaged by radiation. RNA sequencing (RNA-Seq) using Lin − c-Kit + cell populations revealed the mechanism by which inhibition of Caspase-1 mitigates post-irradiation hematopoietic stem cell damage....