Centre for Reproductive Health, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia; Department of Molecular and Translational Sciences, Monash University, Melbourne, VIC 3800, Australia; University of Melbourne Centre for Cancer Research, University of Melbourne, Melbourne, VIC 3000, Australia; Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia.
Centre for Reproductive Health, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia; Department of Molecular and Translational Sciences, Monash University, Melbourne, VIC 3800, Australia.
Stem Cell Reports. 2024 Oct 8;19(10):1379-1388. doi: 10.1016/j.stemcr.2024.08.011. Epub 2024 Sep 26.
Spermatogonial stem cells (SSCs) are essential for sustained sperm production, but SSC regulatory mechanisms and markers remain poorly defined. Studies have suggested that the Id family transcriptional regulator Id4 is expressed in SSCs and involved in SSC maintenance. Here, we used reporter and knockout models to define the expression and function of Id4 in the adult male germline. Within the spermatogonial pool, Id4 reporter expression and inhibitor of DNA-binding 4 (ID4) protein are found throughout the GFRα1+ fraction, comprising the self-renewing population. However, Id4 deletion is tolerated by adult SSCs while revealing roles in meiotic spermatocytes. Cultures of undifferentiated spermatogonia could be established following Id4 deletion. Importantly, ID4 loss in undifferentiated spermatogonia triggers ID3 upregulation, and both ID proteins associate with transcription factor partner TCF3 in wild-type cells. Combined inhibition of IDs in cultured spermatogonia disrupts the stem cell state and blocks proliferation. Our data therefore demonstrate critical but functionally redundant roles of IDs in SSC function.
精原干细胞（SSCs）对于持续的精子产生至关重要，但 SSC 的调节机制和标志物仍未得到充分定义。研究表明，Id 家族转录调节因子 Id4 在 SSCs 中表达，并参与 SSC 的维持。在这里，我们使用报告基因和敲除模型来定义 Id4 在成年雄性生殖系中的表达和功能。在精原细胞池中，Id4 报告基因表达和 DNA 结合抑制因子 4（ID4）蛋白在整个 GFRα1+ 部分中均有发现，该部分包含自我更新的群体。然而，Id4 缺失在成年 SSCs 中是可以耐受的，同时揭示了在减数分裂精母细胞中的作用。Id4 缺失后可以建立未分化精原细胞的培养物。重要的是，未分化精原细胞中 ID4 的缺失会触发 ID3 的上调，并且这两种 ID 蛋白在野生型细胞中与转录因子伴侣 TCF3 结合。在培养的精原细胞中联合抑制 IDs 会破坏干细胞状态并阻止增殖。因此，我们的数据表明 IDs 在 SSC 功能中具有关键但功能冗余的作用。
