Chen Junhua, Cen Changhuo, Wang Mengyue, Qin Shanshan, Liu Bowen, Shen Zhiming, Cui Xiuhong, Hou Xiaohui, Gao Fei, Chen Min
Department of Cell Biology, Zunyi Medical University, Zunyi, Guizhou 563000, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
J Genet Genomics. 2025 May;52(5):680-688. doi: 10.1016/j.jgg.2024.12.006. Epub 2024 Dec 15.
Sertoli and granulosa cells, the initial differentiated somatic cells in bipotential gonads, play crucial roles in directing male and female gonad development, respectively. The transcription factor Foxo1 is involved in diverse cellular processes, and its expression in gonadal somatic cells is sex-dependent. While Foxo1 is abundantly expressed in ovarian granulosa cells, it is notably absent in testicular Sertoli cells. Nevertheless, its function in gonadal somatic cell differentiation remains elusive. In this study, we find that ectopic expression of Foxo1 in Sertoli cells leads to defects in testes development. Further study uncovers that the ectopic expression of Foxo1 induces the abundant expression of Foxl2 in Sertoli cells, along with the upregulation of other female-specific genes. In contrast, the expression of male-specific genes is reduced. Mechanistic studies indicate that Foxo1 directly binds to the promoter region of Foxl2, inducing its expression. Our findings highlight that Foxo1 serves as a key regulator for the lineage maintenance of ovarian granulosa cells. This study contributes valuable insights into understanding the regulatory mechanisms governing the lineage maintenance of gonadal somatic cells.
支持细胞和颗粒细胞是双潜能性腺中最初分化的体细胞，分别在引导雄性和雌性性腺发育中发挥关键作用。转录因子Foxo1参与多种细胞过程，其在性腺体细胞中的表达具有性别依赖性。虽然Foxo1在卵巢颗粒细胞中大量表达，但在睾丸支持细胞中却明显缺失。然而，其在性腺体细胞分化中的功能仍不清楚。在本研究中，我们发现Foxo1在支持细胞中的异位表达导致睾丸发育缺陷。进一步研究发现，Foxo1的异位表达诱导了支持细胞中Foxl2的大量表达，同时其他雌性特异性基因也上调。相反，雄性特异性基因的表达减少。机制研究表明，Foxo1直接结合Foxl2的启动子区域，诱导其表达。我们的研究结果突出表明，Foxo1是卵巢颗粒细胞谱系维持的关键调节因子。这项研究为理解性腺体细胞谱系维持的调控机制提供了有价值的见解。
