Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China.
PLoS Genet. 2021 Sep 7;17(9):e1009778. doi: 10.1371/journal.pgen.1009778. eCollection 2021 Sep.
Meiosis initiation and progression are regulated by both germ cells and gonadal somatic cells. However, little is known about what genes or proteins connecting somatic and germ cells are required for this regulation. Our results show that deficiency for adhesion molecule IGSF11, which is expressed in both Sertoli cells and germ cells, leads to male infertility in mice. Combining a new meiotic fluorescent reporter system with testicular cell transplantation, we demonstrated that IGSF11 is required in both somatic cells and spermatogenic cells for primary spermatocyte development. In the absence of IGSF11, spermatocytes proceed through pachytene, but the pericentric heterochromatin of nonhomologous chromosomes remains inappropriately clustered from late pachytene onward, resulting in undissolved interchromosomal interactions. Hi-C analysis reveals elevated levels of interchromosomal interactions occurring mostly at the chromosome ends. Collectively, our data elucidates that IGSF11 in somatic cells and germ cells is required for pericentric heterochromatin dissociation during diplotene in mouse primary spermatocytes.
减数分裂的启动和进程既受生殖细胞又受性腺体细胞的调控。然而,对于连接体细胞和生殖细胞的哪些基因或蛋白对于这种调控是必需的,人们知之甚少。我们的研究结果表明,黏附分子 IGSF11 在支持细胞和生殖细胞中均有表达,其缺失会导致小鼠雄性不育。我们结合新的减数分裂荧光报告系统和睾丸细胞移植,证明 IGSF11 对于精原细胞发育既在体细胞中又在生殖细胞中是必需的。在 IGSF11 缺失的情况下,精母细胞可以通过粗线期,但从晚粗线期开始,非同源染色体的着丝粒异染色质仍不适当聚集,导致染色体间相互作用未被解开。Hi-C 分析显示,染色体间相互作用的水平升高,主要发生在染色体末端。总的来说,我们的数据阐明了体细胞和生殖细胞中的 IGSF11 对于小鼠初级精母细胞在双线期着丝粒异染色质解聚是必需的。