| First Author | Zhou C | Year | 2024 |
| Journal | Cell Stem Cell | Volume | 31 |
| Issue | 9 | Pages | 1359-1375.e8 |
| PubMed ID | 38955185 | Mgi Jnum | J:361410 |
| Mgi Id | MGI:7704965 | Doi | 10.1016/j.stem.2024.06.007 |
| Citation | Zhou C, et al. (2024) Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening. Cell Stem Cell |
| abstractText | 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. |
