RNA-seq analysis of Control and Mps1sKO testis at P10

Monopolar spindle 1 (Mps1), which plays a critical role in somatic mitosis, has also been revealed to be essential for meiosis I in oocytes. Spermatogenesis is an important process involving successive mitosis and meiosis, but the function of Mps1 in spermatogenesis remains unclear. Here, we generated Mps1 conditional knockout mice and found that Ddx4-cre-driven loss of Mps1 in male mice resulted in depletion of undifferentiated spermatogonial cells and subsequently of differentiated spermatogonia and spermatocytes. In addition, Stra8-cre-driven ablation of Mps1 in male mice led to germ cell loss and fertility reduction. Spermatocytes lacking Mps1 were blocked at the zygotene-to-pachytene transition in prophase of meiosis I, and the expression of many meiotic genes was decreased, while that of apoptotic genes was increased. Moreover, we also detected increased apoptosis in spermatocytes with Mps1 knockout, which may have been the reason why germ cells were lost. Taken together, our findings indicate that Mps1 is required for mitosis of gonocytes and spermatogonia, differentiation of undifferentiated spermatogonia, and progression of meiosis I in spermatocytes. We sequenced the testis mRNA from both control mice and Mps1sKO mice at P10. Two biological replicates were generated per condition.单极纺锤体1（Monopolar spindle 1，Mps1）在体细胞有丝分裂中发挥关键作用，同时也被证实对卵母细胞的减数分裂I期至关重要。精子发生是一个涉及连续有丝分裂与减数分裂的重要过程，但Mps1在精子发生中的功能仍不明确。本研究构建了Mps1条件性基因敲除小鼠（conditional knockout mice），发现雄性小鼠体内由Ddx4-cre介导的Mps1缺失会导致未分化精原细胞耗竭，随后分化精原细胞与精母细胞也随之减少。此外，雄性小鼠体内由Stra8-cre介导的Mps1敲除会引发生殖细胞丢失与生育能力下降。缺失Mps1的精母细胞会阻滞在减数分裂I期前期的偶线期至粗线期转换阶段，同时大量减数分裂相关基因的表达水平下调，而凋亡相关基因的表达水平则上调。此外，本研究还检测到Mps1敲除的精母细胞凋亡水平升高，这可能是生殖细胞丢失的原因。综上，本研究结果表明，Mps1对于生殖母细胞与精原细胞的有丝分裂、未分化精原细胞的分化，以及精母细胞的减数分裂I期进程均不可或缺。本研究对出生后第10天（P10）的对照组小鼠与Mps1条件性敲除（Mps1sKO）小鼠的睾丸mRNA进行了测序，每组设置2个生物学重复样本。