利用小鼠及斑马鱼模型研究造血干细胞衰老过程的表观遗传学调控

Ageing is an important question for both developmental biology and human health field. As one of the most well-studied adult stem cells, hematopoietic stem cells (HSCs) provide an excellent opportunity to understand the epigenetic regulation mechanism of ageing at both stem cell and individual level. To accomplish this goal, we are going to establish mouse and zebrafish HSCs ageing analysis platforms. Using zebrafish transgenic models, low cell number ATAC-seq technique , ChIP-seq technique and ageing analysis platform, we would be able to understand the epigenetic regulation network of Bmi1 and Ezh2 in ageing. We will also try to demonstrate the variable epigenetic pattern during HSCs ageing, explore novel epigenetic markers and critical regulators for ageing, and analyze their regulation network. This study will also provide HSCs ageing animal models for future studies and chemical screening.

研究组织干细胞衰老对于理解个体衰老有重要意义。造血干细胞作为研究最为透彻的组织干细胞之一，明确其衰老过程及这一过程的表观遗传调控机制具有重大科学和现实意义。本项目将建立小鼠与斑马鱼两套造血干细胞（HSCs）衰老分析系统。利用转基因斑马鱼模型，结合低起始量细胞开放染色质定位测序和ChIP-seq技术手段，研究关键表观因子Bmi1和Ezh2在HSCs衰老中的功能及其调控网络。项目将发掘新的HSCs衰老的表观遗传标记物，寻找新的调控HSCs衰老的关键表观遗传因子，分析它们在HSCs衰老和相关血液疾病发生中的功能，探讨它们参与的调控网络。研究将尝试在单细胞水平上分析HSCs衰老的表观遗传学变化。项目还将构建HSCs衰老动物模型，为寻找干预HSCs衰老的小分子化合物／天然药物提供筛选平台基础。

研究组织干细胞衰老对于理解个体衰老有重要意义，明确其衰老过程及这一过程的表观遗传调控机制具有重大科学和现实意义。本项目建立了斑马鱼造血干细胞(HSCs)衰老分析系统，并利用斑马鱼模型，结合多组学手段，研究表观遗传调控关键基因在HSCs衰老中的功能及其调控网络，并发掘了新的HSCs衰老的表观遗传关键因子，项目寻找到新的参与HSCs发育与衰老调控的代谢关键基因及调控网络，并构建了HSC衰老斑马鱼模型，为干预HSCs衰老的代谢小分子及天然药物提供了筛选平台。除对造血干细胞衰老的表观遗传学研究外，项目还利用斑马鱼和小鼠模型，探讨了颅颌面发育和关节炎发病中的表观遗传调控机制。