Study the generality of asymmetric histone inheritance

 描述（申请人提供）：研究不对称组蛋白遗传的一般性项目概述：表观遗传现象是通过细胞分裂而不改变初级DNA序列的基因表达或功能的可遗传变化。重要的是，表观遗传信息指导具有相同基因组的细胞成为多细胞生物（包括人类）中不同的细胞类型。干细胞具有独特的自我更新和产生多种分化细胞类型的能力。干细胞命运的错误决定和干细胞衍生物的功能障碍是许多人类疾病的常见原因。然而，一个长期存在的问题是干细胞如何在许多细胞分裂过程中保留其表观遗传记忆，以及适当的干细胞表观遗传信息的丢失是否会导致疾病？许多类型的干细胞经历不对称的细胞分裂，产生具有不同细胞命运的子细胞：一个保留干细胞身份，另一个分化。最近，我们发现在果蝇雄性生殖干细胞（GSC）的不对称分裂过程中，预先存在的组蛋白3（H3）被选择性地分离到GSC中，而新合成的H3则富集在分化的子细胞中。由于组蛋白的翻译后修饰是表观遗传信息的关键组成部分，因此我们的研究提供了第一个直接证据，表明干细胞可能选择性地保留定义其干细胞身份的预先存在的组蛋白。我们现在正处于一个独特的位置，探索这一有趣现象的普遍性，以调查它是否适用于其他组蛋白，其他 成体干细胞和其他物种。这些研究将使我们了解这是否是细胞在发育和稳态过程中具有不同命运的一般机制，这将为探索表观遗传调控的生物学意义和人类健康相关性提供前所未有的基础。

 DESCRIPTION (provided by applicant): Study the generality of asymmetric histone inheritance Project Summary: Epigenetic phenomena are heritable changes in gene expression or function through cell divisions without altering primary DNA sequences. Importantly, it is the epigenetic information that directs cells with identical genomes to become distinct cell types in multicellular organisms, including humans. Stem cells are unique in their abilities to both self-renew and give rise to a variety of differentiated cell types. Mis-determination of stem cell fate and malfunction of stem cell derivatives are common causes of many human diseases. However, a long-standing question has been how stem cells retain their epigenetic memory throughout many cell divisions, and, does the loss of proper stem cell epigenetic information lead to diseases? Many types of stem cells undergo asymmetric cell divisions to give rise to daughter cells with distinct cell fates: one that retains stem cell identity and another that differentiates. Recently, we found that during the asymmetric division of Drosophila male germline stem cell (GSC), the preexisting histone 3 (H3) is selectively segregated to the GSC whereas newly synthesized H3 is enriched in the differentiating daughter cell. Since post-translational modification of histones is a key component of epigenetic information, our studies provide the first direct evidence suggesting that stem cells may selectively retain preexisting histones that define its stem cell identity. We are now at a unique position to explore the generality of this intriguing phenomenon to investigate whether it applies to other histones, other adult stem cells, and in other species. These studies will allow us to understand whether this is a general mechanism for cells to have distinct fates during development and homeostasis, which will provide an unprecedented foundation to explore the biological significance and human health relevance of epigenetic regulation.