Bud31-mediated alternative splicing is required for spermatogonial stem cell self-renewal and differentiation
Bud31-mediated alternative splicing is required for spermatogonial stem cell self-renewal and differentiation
复制标题
DOI：
10.1038/s41418-022-01057-1
复制
发表时间：
2022-09
影响因子：
12.4
通讯作者：
J. Qin;Tao Huang;Zixiang Wang;Xiyu Zhang;Jing Wang;Qianli Dang;Donghai Cui;Xinyu Wang;Yunjiao Zhai;Ling Zhao;Gang Lu;C. Shao;Shi-Zhen Li;Hongbin Liu;Zhaojian Liu
中科院分区：
文献类型：
--
作者：
J. Qin;Tao Huang;Zixiang Wang;Xiyu Zhang;Jing Wang;Qianli Dang;Donghai Cui;Xinyu Wang;Yunjiao Zhai;Ling Zhao;Gang Lu;C. Shao;Shi-Zhen Li;Hongbin Liu;Zhaojian Liu
选择性剪接（AS）在细胞分化和发育过程中受到严格调控。AS事件在睾丸中普遍存在，但精子发生中的剪接调控仍不清楚。在这里，我们报告剪接体组件Bud 31在小鼠精子发生过程中起着至关重要的作用。生殖细胞特异性敲除Bud 31导致精原细胞丢失和男性不育。我们进一步证明了Bud 31是维持精原干细胞库和启动精子发生所必需的。SMART-seq显示，在生殖细胞中Bud 31的缺失导致广泛的外显子跳跃和内含子保留。特别地，我们发现Cdk 2是Bud 31的直接剪接靶点之一，Bud 31的敲除导致Cdk 2的第一内含子的保留，从而导致Cdk 2的表达降低。我们的研究结果表明，Bud 31介导的AS内精原干细胞调节自我更新和分化的雄性生殖细胞在哺乳动物。
Alternative splicing (AS) is tightly regulated during cell differentiation and development. AS events are prevalent in the testis, but the splicing regulation in spermatogenesis remains unclear. Here we report that the spliceosome component Bud31 plays a crucial role during spermatogenesis in mice. Germ cell-specific knockout ofBud31led to loss of spermatogonia and to male infertility. We further demonstrate that Bud31 is required for both spermatogonial stem cell pool maintenance and the initiation of spermatogenesis. SMART-seq revealed that deletion ofBud31in germ cells causes widespread exon-skipping and intron retention. Particularly, we identifiedCdk2as one of the direct splicing targets of Bud31, knockout ofBud31resulted in retention of the first intron ofCdk2, which led to a decrease in Cdk2 expression. Our findings suggest that Bud31-mediated AS within spermatogonial stem cells regulates the self-renewal and differentiation of male germ cells in mammals.