重庆医科大学侯宇教授等共同合作，近期取得重要工作进展，他们研究提出，Nynrin通过抑制线粒体通透性转换孔的开放来保护造血干细胞的功能。相关研究成果2024年7月1日在线出版于《细胞—干细胞》上。

据介绍，线粒体是造血干细胞（HSC）稳态的关键调节因子。

研究人员发现，转录因子Nynrin是通过调节线粒体功能来维持HSC的关键调节因子。在稳态和应激条件下，Nynrin在HSC中高度表达。敲除Nynrin降低了HSC的频率、休眠和自我更新，线粒体功能障碍增加，表现为异常mPTP开放、线粒体肿胀和ROS水平升高。这些变化降低了HSC的辐射耐受性，并促进了坏死样表型。相反，HSC中Nynrin的过度表达降低了辐射（IR）诱导的致死性。Nynrin的缺失激活Ppif，导致亲环蛋白D（CypD）的过度表达和进一步的线粒体功能障碍。Ppif单倍体剂量不足或CypD的药理学抑制等策略可显著减轻这些影响，恢复Nynrin缺陷小鼠的HSC功能。

总之，这一研究确定Nynrin是HSC线粒体功能的关键调节因子，突出了在癌症治疗期间保持干细胞活力的潜在治疗靶点。

附：英文原文

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

Author: Chengfang Zhou, Mei Kuang, Yin Tao, Jianming Wang, Yu Luo, Yinghao Fu, Zhe Chen, Yuanyuan Liu, Zhigang Li, Weiru Wu, Li Wang, Ying Dou, Junping Wang, Yu Hou

Issue&Volume: 2024-07-01

Abstract: 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.

DOI: 10.1016/j.stem.2024.06.007

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00215-7