{Reference Type}: Journal Article
{Title}: Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.
{Author}: Zhou C;Kuang M;Tao Y;Wang J;Luo Y;Fu Y;Chen Z;Liu Y;Li Z;Wu W;Wang L;Dou Y;Wang J;Hou Y;
{Journal}: Cell Stem Cell
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 25
{Factor}: 25.269
{DOI}: 10.1016/j.stem.2024.06.007
{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.