Статья

Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening

Chengfang ZhouDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaMei KuangDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaTao YinDepartment of Gynecology, The affiliated ZhuZhou Hospital (ZhuZhou Central Hospital), Xiangya Medical College of Central South University, Zhuzhou, Hunan 412007, ChinaJianming WangDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaJianming WangDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaYu LuoDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaYinghao FuDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaZhe ChenDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaYuanyuan LiuDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaZhigang LiDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaWeiru WuDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaLi WangDepartment of Hematology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong Qu, Chongqing 400016, ChinaYing DouDepartment of Hematology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China. Electronic address: [email protected]Junping WangDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, ChinaYu HouDepartment of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; Department of Hematology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University, Chongqing 400016, China. Electronic address: [email protected]

2024en

ABI

Аннотация

Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.

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Идентификаторы

DOI: 10.1016/j.stem.2024.06.007

Цитирования и источники

Цитирований: 2Использованных источников: 0

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