MYSM1表观调控间充质干细胞的免疫调控功能及在免疫相关疾病防治中的应用研究

间充质干细胞（MSC）是一种重要的免疫调节细胞，虽然MSC的应用越来越广泛，但它的免疫调控能力不稳定，调控分子机制并不清楚。我们已发表的工作（Immunity, 2011，IF=24）首次表明组蛋白H2A去泛素化酶MYSM1调控造血细胞的发育和功能。MYSM1 对MSC功能的影响目前还未见报道。我们的初步研究结果提示过表达MYSM1后，MSC的免疫抑制作用更强、更稳定。为此本课题拟借助慢病毒干扰或过表达MYSM1及相关动物模型，细致研究MYSM1对MSC免疫调控功能的影响，通过ChIP实验和深度测序技术的高通量全基因组扫描芯片深入探讨可能的调节机制及MYSM1 的可能作用靶基因，研究修饰后MSC用于免疫相关疾病防治的优越性。本课题有助于加深对MYSM1及其整个家族的生理学功能的了解，从表观遗传和染色质水平了解MSC的免疫调控功能，为MSC应用于免疫相关疾病的防治提供新的理论指导。

Mesenchymal stem cells (MSCs) have been shown to be kind of important immunoregulatory cells. In spite of the broad application, the molecular mechanism of their immunoregulatory function is largely unknown. Our published data (Immunity, 2011), for the first time, showed histone H2A deubiquitinase MYSM1 controlled the generation and function of hematopoietic cells. So far, the influence of MYSM1 on the function of MSCs remains unknown. Our preliminary data indicated that MSCs showed stronger and more stable immunoregulatory function after over expression of MYSM1 in MSCs. Hence, this proposed study will mechanistically investigate the immunoregulatory function of MSC through silencing or over expression MYSM1 and studying the related animal model. ChIP-seq and RNA-seq experiments will use to elucidate the target gene of MYSM1.This study will help to determine the physiological function of MYSM1, thus contribute to a fundamental understanding of the biological function for the entire group of newly identified histone deubiquitinases. This study will also shed light on the fundamental understanding of the immunomodulatory ability of MSCs at the epigenetic and chromatin level. Finally, this study will provide new theoretical guidance for the clinical application of MSCs.