Zheng Yu, Phillips LeAnna J, Hartman Rachel, An Junhui, Dann Christina T
Department of ChemistryIndiana University, Bloomington, Indiana, USA.
Department of ChemistryIndiana University, Bloomington, Indiana, USA
Reproduction. 2016 Oct;152(4):363-77. doi: 10.1530/REP-16-0140. Epub 2016 Aug 2.
Expression levels of the pluripotency determinant, POU5F1, are tightly regulated to ensure appropriate differentiation during early embryogenesis. POU5F1 is also present in the spermatogonial stem cell/progenitor cell population in mice and it is downregulated as spermatogenesis progresses. To test if POU5F1 downregulation is required for SSCs to differentiate, we produced transgenic mice that ubiquitously express POU5F1 in Cre-expressing lineages. Using a Vasa-Cre driver to produce ectopic POU5F1 in all postnatal germ cells, we found that POU5F1 downregulation was necessary for spermatogonial expansion during the first wave of spermatogenesis and for the production of differentiated spermatogonia capable of undergoing meiosis. In contrast, undifferentiated spermatogonia were maintained throughout adulthood, consistent with a normal presence of POU5F1 in these cells. The results suggest that POU5F1 downregulation in differentiating spermatogonia is a necessary step for the progression of spermatogenesis. Further, the creation of a transgenic mouse model for conditional ectopic expression of POU5F1 may be a useful resource for studies of POU5F1 in other cell lineages, during tumorogenesis and cell fate reprogramming.
多能性决定因子POU5F1的表达水平受到严格调控，以确保早期胚胎发育过程中的适当分化。POU5F1也存在于小鼠的精原干细胞/祖细胞群体中，并且随着精子发生的进行而被下调。为了测试SSCs分化是否需要POU5F1下调，我们构建了在表达Cre的谱系中普遍表达POU5F1的转基因小鼠。使用Vasa-Cre驱动子在所有出生后的生殖细胞中产生异位POU5F1，我们发现POU5F1下调对于精子发生第一波期间的精原细胞扩增以及产生能够进行减数分裂的分化精原细胞是必要的。相反，未分化的精原细胞在整个成年期都得以维持，这与这些细胞中正常存在POU5F1一致。结果表明，分化中的精原细胞中POU5F1下调是精子发生进程的必要步骤。此外，构建用于POU5F1条件性异位表达的转基因小鼠模型可能是研究POU5F1在其他细胞谱系、肿瘤发生和细胞命运重编程过程中的有用资源。
