Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC 3010, Australia.
Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.
Cells. 2024 Mar 12;13(6):494. doi: 10.3390/cells13060494.
Stem cell maintenance and differentiation can be regulated via the differential activity of transcription factors within stem cells and their progeny. For these factors to be active, they need to be transported from their site of synthesis in the cytoplasm into the nucleus. A tissue-specific requirement for factors involved in nuclear importation is a potential mechanism to regulate stem cell differentiation. We have undertaken a characterization of male sterile importin alpha 1 () null alleles in and found that Dα1 is required for maintaining germline stem cells (GSCs) in the testis niche. The loss of GSCs can be rescued by ectopic expression of Dα1 within the germline but the animals are still infertile, indicating a second role for Dα1 in spermatogenesis. Expression of a Dα1 dominant negative transgene in GSCs confirmed a functional requirement for Dα1 in GSC maintenance but expression of the transgene in differentiating spermatogonia did not exhibit a phenotype indicating a specific role for Dα1 within GSCs. Our data indicate that Dα1 is utilized as a regulatory protein within GSCs to facilitate nuclear importation of proteins that maintain the stem cell pool.
干细胞的维持和分化可以通过转录因子在干细胞及其后代中的差异活性来调节。为了使这些因子发挥作用,它们需要从细胞质中的合成部位运输到细胞核中。核输入中涉及的因子的组织特异性要求是调节干细胞分化的潜在机制。我们对 中的雄性不育导入素 α1 ( ) 缺失等位基因进行了表征,发现 Dα1 是维持睾丸龛中生殖干细胞 (GSCs) 所必需的。GSCs 的缺失可以通过在生殖系内异位表达 Dα1 来挽救,但动物仍然不育,这表明 Dα1 在精子发生中具有第二个作用。在 GSCs 中表达 Dα1 显性负转录本证实了 Dα1 在 GSC 维持中的功能需求,但在分化的精原细胞中表达该转录本并未表现出表型,表明 Dα1 在 GSCs 中具有特定作用。我们的数据表明,Dα1 被用作 GSCs 中的调节蛋白,以促进维持干细胞池的蛋白质的核输入。