Department of Animal Sciences, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI 48824, USA.
Department of Animal Sciences, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI 48824, USA.
Stem Cell Reports. 2024 Nov 12;19(11):1548-1563. doi: 10.1016/j.stemcr.2024.09.006. Epub 2024 Oct 10.
At different stages of spermatogenesis, germ cell mitochondria differ remarkably in morphology, architecture, and functions. However, it remains elusive how mitochondria change their features during spermatogonial differentiation, which in turn impacts spermatogonial stem cell fate decision. In this study, we observed that mitochondrial fusion and fission were both upregulated during spermatogonial differentiation. As a result, the mitochondrial morphology remained unaltered. Enhanced mitochondrial fusion and fission promoted spermatogonial differentiation, while the deficiency in DRP1-mediated fission led to a stage-specific blockage of spermatogenesis at differentiating spermatogonia. Our data further revealed that increased expression of pro-fusion factor MFN1 upregulated mitochondrial metabolism, whereas DRP1 specifically regulated mitochondrial permeability transition pore opening in differentiating spermatogonia. Taken together, our findings unveil how proper spermatogonial differentiation is precisely controlled by concurrently accelerated and properly balanced mitochondrial fusion and fission in a germ cell stage-specific manner, thereby providing critical insights about mitochondrial contribution to stem cell fate decision.
在精子发生的不同阶段，精母细胞线粒体在形态、结构和功能上有显著差异。然而，线粒体在精原细胞分化过程中如何改变其特征，进而影响精原干细胞命运决定，这仍然难以捉摸。在这项研究中，我们观察到线粒体融合和裂变在精原细胞分化过程中均上调。结果，线粒体形态保持不变。增强的线粒体融合和裂变促进了精原细胞分化，而 DRP1 介导的裂变缺陷导致分化的精原细胞中出现特定阶段的精子发生阻滞。我们的数据进一步表明，促融合因子 MFN1 的表达增加上调了线粒体代谢，而 DRP1 特异性调节分化的精原细胞中线粒体通透性转换孔的开放。总之，我们的研究结果揭示了适当的精原细胞分化是如何通过在特定的生殖细胞阶段以协调加速和适当平衡的方式精确控制的，从而为线粒体对干细胞命运决定的贡献提供了重要的见解。
