<i>Foxo1</i> directs the transdifferentiation of mouse Sertoli cells into granulosa-like cells

Junhua Chen; Changhuo Cen; Mengyue Wang; Shanshan Qin; Bowen Liu; Zhiming Shen; Xiuhong Cui; Xiaohui Hou; Fei Gao; Min Chen

doi:10.1016/j.jgg.2024.12.006

Volume 52 Issue 5

May 2025

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Article Navigation > Journal of Genetics and Genomics > 2025 > 52(5): 680-688

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

doi: 10.1016/j.jgg.2024.12.006

Junhua Chen^a,
Changhuo Cen^b,c,d,e,
Mengyue Wang^b,c,d,e,
Shanshan Qin^f,
Bowen Liu^b,c,d,e,
Zhiming Shen^b,c,d,e,
Xiuhong Cui^b,c,d,e,
Xiaohui Hou^a,
Fei Gao^b,c,d,e,
Min Chen^b,c,d,e

a. Department of Cell Biology, Zunyi Medical University, Zunyi, Guizhou 563000, China;
b. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;
c. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China;
d. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China;
e. University of Chinese Academy of Sciences, Beijing 100049, China;
f. Lin He's Academician Workstation of New Medicine and Clinical Translation, Jining Medical University, Jining, Shandong 272000, China

Funds:

This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB0820000), the National Natural Science Foundation of China (82421003, 32270902, 32170855), the Faculty Resources Project of the College of Life Sciences, Inner Mongolia University (2022-104), and Initiative Scientific Research Program, Institute of Zoology, Chinese Academy of Sciences (2023IOZ0102).

Received Date: 2024-12-03
Accepted Date: 2024-12-09
Rev Recd Date: 2024-12-08

Available Online: 2025-07-11

Publish Date: 2024-12-15

Abstract

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.
- Foxo1,
- Foxl2,
- Sertoli cell,
- Granulosa cell,
- Transdifferentiation

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