中国科学院动物研究所陈敏等研究人员合作发现，Foxo1引导小鼠塞尔托利氏细胞向类颗粒细胞的转分化。这一研究成果于2024年12月15日在线发表在国际学术期刊《遗传学报》上。

研究人员发现，Foxo1在塞尔托利氏细胞中的异位表达导致睾丸发育缺陷。进一步研究揭示，Foxo1的异位表达诱导了Foxl2在塞尔托利氏细胞中的大量表达，并上调了其他雌性特异性基因。相反，雄性特异性基因的表达则减少。机制研究表明，Foxo1直接结合到Foxl2的启动子区域，诱导其表达。

该研究强调了Foxo1作为卵巢颗粒细胞谱系维持的关键调节因子。并且，该研究为理解性腺体细胞谱系维持的调控机制提供了宝贵的见解。

据介绍，塞尔托利氏细胞和颗粒细胞是双潜能性性腺中最初分化的体细胞，分别在雄性和雌性性腺的发育中发挥着关键作用。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。尽管Foxo1在卵巢颗粒细胞中高度表达，但在睾丸塞尔托利氏中则明显缺失。然而，Foxo1在性腺体细胞分化中的功能仍不明确。

附：英文原文

Title: Foxo1 directs the transdifferentiation of mouse Sertoli cells into granulosa-like cells

Author: Xiaohui Hou a, Fei Gao b c d e, Min Chen b c d e

Issue&Volume: 2024/12/15

Abstract: 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.

DOI: 10.1016/j.jgg.2024.12.006

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724003552