Transcriptome analysis of Prdm10 maternal knock out mouse oocytes

PRDM proteins are metazoan specific transcriptional regulators that play diverse roles in mammalian development and disease. Several members such as PRDM1, PRDM14 and PRDM9, have been implicated in germ cell formation and homeostasis and are essential to fertility-related processes. Others, such as PRDM14, PRDM15 and PRDM10 play a role in early embryogenesis and embryonic stem cell maintenance. Here, we reveal an additional maternal requirement for PRDM10 . Absence of maternal Prdm10 results in catastrophic failure of oocyte-to-embryo transition and complete arrest at the 2-cell stage. We describe multiple defects in oocytes, zygotes and 2-cell stage embryos relating to the failure to accumulate PRDM10 target gene transcripts in the egg. Transcriptomic analysis and integration of genome-wide chromatin-binding data reveals novel, essential PRDM10 targets, including the cytoskeletal protein SEPTIN11. We demonstrate that the failure to express maternal Septin11, in the absence of maternal PRDM10, disrupts Septin-complex assembly at the polar body extrusion site in MII oocytes. Our study sheds light into the essentiality of maternal PRDM10, the requirement of the maternal Septin-complex and the likely evolutionary conservation of this regulatory axis in human female germ cells.PRDM蛋白是后生动物（metazoan）特异性的转录调控因子，在哺乳动物发育与疾病进程中发挥多样化功能。其中PRDM1、PRDM14与PRDM9等多个家族成员已被证实参与生殖细胞形成与稳态维持，且对生育相关进程至关重要。而PRDM14、PRDM15与PRDM10等成员则参与早期胚胎发生与胚胎干细胞维持。本研究揭示了PRDM10的另一项母源调控需求。母源Prdm10缺失会导致卵母细胞向胚胎转化过程出现灾难性障碍，并使胚胎完全停滞于2细胞期。本研究观察到卵母细胞、受精卵（zygotes）与2细胞期胚胎存在多种缺陷，其根源为卵内无法积累PRDM10靶基因的转录本。转录组分析结合全基因组染色质结合数据，鉴定出一系列全新且必需的PRDM10靶基因，其中包括细胞骨架蛋白SEPTIN11。本研究证实，在母源PRDM10缺失的情况下，母源Septin11表达缺失会破坏MII期卵母细胞（MII oocytes）极体排出位点的Septin复合物组装。本研究阐明了母源PRDM10的必需性、母源Septin复合物的功能需求，以及该调控轴在人类雌性生殖细胞中可能存在的进化保守性。