%0 Journal Article
%T Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.
%A Zhou C
%A Kuang M
%A Tao Y
%A Wang J
%A Luo Y
%A Fu Y
%A Chen Z
%A Liu Y
%A Li Z
%A Wu W
%A Wang L
%A Dou Y
%A Wang J
%A Hou Y
%J Cell Stem Cell
%V 0
%N 0
%D 2024 Jun 25
%M 38955185
%F 25.269
%R 10.1016/j.stem.2024.06.007
%X 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.