202209Shimada

研究発表を行った学会；
Gordon Research Seminar; mammalian reproduction. （Poster発表）
2022年8月13-14日　（バーモント州Dover Mt.Snow, USA）
Gordon Research Conference; mammalian reproduction. （Oral発表）
2022年8月14-19日　（バーモント州Dover Mt.Snow, USA）
タイトル； STRA8-Rb interaction initiates S phase entry and meiosis in female germ cells.
発表者；島田　龍輝氏
（熊本大学　発生医学研究所　染色体制御分野）
要旨；
Meiosis starts from one round of DNA replication followed by two round of cell division, so that mitosis-meiosis transition occurs in S phase. Previously, we have reported that STRA8-MEIOSIN activates meiotic genes, which is a critical step for the meiotic initiation. However, it is still unclear how meiotic gene activation is coincided with S phase. We identified the retinoblastoma family protein, RB1 and p107 (RB-like 1) as STRA8 interacting proteins. RB is known as a repressor of S phase entry. To study the physiological relevance of STRA8-RB interaction, we generated mutant mice that express STRA8 lacking LXCXE motif (Stra8ΔRB), in which STRA8 cannot bind to RB but preserves intact interaction with MEIOSIN. In Stra8ΔRB mutant mice, whereas male mice produce functional sperm, female prematurely lose oocytes in adult stage. To address the role of RB-STRA8 interaction in meiotic initiation, we conducted single cell-RNA-sequencing analyses using STRA8-expressing cells from, control, Stra8ΔRB and STRA8-null ovaries. Transcriptome analysis revealed that STRA8-null cells highly expressed pluripotent genes, suggesting STRA8 functions to induce differentiation prior to meiosis. We also revealed that without RB-STRA8 interaction, S phase entry and expression of the Meiosin were compromised. As a result, meiosis progression was delayed in Stra8∆RB germ cells. Our present data suggests that STRA8 have central role to induce cell differentiation, S phase entry and meiotic initiation to ensure production of functional oocytes.