BMI1 promotes spermatogonial stem cell maintenance by epigenetically repressing Wnt10b/β-catenin signaling.

Jun Yu, Cong Shen, Meng Lin, Xia Chen, Xiuliang Dai, Zhiran Li, Yunhao Wu, Yangbo Fu, Jinxing Lv, Xiaoyan Huang, Bo Zheng, Fei Sun

International journal of biological sciences 2022

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The self-renewal of spermatogonial stem cells (SSCs) requires a special microenvironment and is strictly controlled. Previously, we identified BMI1 as a key regulator of spermatogenesis in a knock-out mouse model. However, the mechanisms by which BMI1 regulates SSC maintenance remain largely unknown. Herein, we show that BMI1 is essential for SSC maintenance. BMI1 directs the transcriptional repression of target genes by increasing H2AK119ub and reducing H3K4me3 in SSCs. Furthermore, BMI1 inhibition resulted in the transcriptional activation of Wnt10b and thereby promoted the nuclear translocation of β-catenin in SSCs. Importantly, the suppression of Wnt/β-catenin signaling restored both the cytoplasmic expression of β-catenin and SSC maintenance in BMI1-deficient SSCs. Finally, we demonstrated that Wnt/β-catenin signaling was also involved in BMI1-mediated SSC maintenance in vivo. Altogether, our study not only reveals a novel mechanism for BMI1 in the process of SSC maintenance, but also provides a potential new strategy for treating male infertility. © The author(s).

Citation

Jun Yu, Cong Shen, Meng Lin, Xia Chen, Xiuliang Dai, Zhiran Li, Yunhao Wu, Yangbo Fu, Jinxing Lv, Xiaoyan Huang, Bo Zheng, Fei Sun. BMI1 promotes spermatogonial stem cell maintenance by epigenetically repressing Wnt10b/β-catenin signaling. International journal of biological sciences. 2022;18(7):2807-2820