在细胞增殖和分化过程中，蕴含表观遗传信息的亲代组蛋白需要回收再组装到复制完成的DNA链上从而传递给子细胞。旧组蛋白的代间传递能否通过其携带的表观遗传信息调控子细胞的命运仍是未知。最新研究发现，在DNA复制过程中MCM2将旧组蛋白分配于DNA滞后链上；果蝇精原干细胞的不对称分裂过程中旧组蛋白富集于子代干细胞中，新合成的组蛋白分配于分化的子细胞中，破坏这一分配方式将导致生殖细胞丢失或肿瘤。基于此，本项目将通过构建MCM2点突变小鼠和精原干细胞模型研究旧组蛋白的分配方式，及其在精原干细胞增殖和分化中的功能。目前我们已成功建立研究新旧组蛋白分配方式的高通量测序eSPAN-CUT & Tag技术，搭建小鼠精原干细胞培养和CRISPER/Cas9基因编辑平台，完成MCM2点突变小鼠的设计。本项目通过研究亲代组蛋白分配在精子发生过程中的作用机制，让我们进一步理解表观遗传调控在配子发生中的作用。

Parental histones are found to recycle and re-assemble to replicated DNA with epigenetic information in daughter cell during proliferation and differentiation. It is still unknown whether the fate of daughter cells could be regulated by parental histone through its epigenetic information. MCM2 is found to transfer and deposit the parental histones on lagging strand during DNA replication. Parental histones are found to enrich in the stem daughter cell, whereas newly synthesized histones are segregated towards the differentiating daughter cell during the asymmetric cell division of Drosophila male germline stem cells. Based on these results, we will use MCM2 point mutation mouse and spermatogonial stem cell models to further study the segregation of parental histone, as well as its role in proliferation and differentiation of mouse spermatogonial stem cell. We have designed a high-throughput sequencing eSPAN-CUT & Tag technology that studying the segregation of parental and newly synthesized histone, established the mouse spermatogonial stem cell culture and CRISPR/Cas9 gene editing platform, and designed MCM2 point mutation mouse. This project will help us to further understand the role of epigenetic regulation in gametogenesis by studying the mechanism of parental histone segregation during spermatogensis.