干细胞及临床转化研究是我国“十三五”期间国家重大科技战略发展计划之一，而干细胞的干性维持是重点部署研究内容。本课题组在研究DLX3单基因突变导致TDO综合征的发病机制时，发现TDO患者的骨髓间充质干细胞（BMSCs）的干性和自我更新能力均强于正常人，患者表现为颅颌面骨密度增龄性增高的临床有利表型。我们结合高通量分析、实时定量PCR和免疫印迹杂交实验结果，提出“TDO综合征致病基因DLX3突变通过调控H19/FGF2/Oct4维持BMSCs干性和自我更新”的科学假设。本项目拟通过细胞、分子、表观调控和基因编辑小鼠层面研究DLX3突变增强BMSCs干性及自我更新的机制。鉴于我国已经步入老龄化社会，老年人骨质健康问题已被社会关注。因此本课题的研究成果将有助于发现新的维持BMSCs干性的方法；理解TDO综合征骨表征的发病机制；及为临床治疗和预防骨质疏松等骨代谢疾病提供思路。

Stem cell and its translation research are one of National Science and Technology Major Project during the national 13th five-year plan. The stemness maintenance of stem cells is the key development area. Our group found TDO patient-derived bone marrow mesenchymal stem cells (TDO-BMSCs) have higher stemness and self-renewal ability compared with BMSCs derived from normal healthy controls, when we investigated the underlying mechanism regarding single gene DLX3 mutation caused TDO syndrome. TDO patients show an accumulating bone density in skull and maxillofacial bone along with an increase in age, which is beneficial to the TDO patients at clinical bone characterization aspect. We did high throughput, real-time PCR and western blot assays and analyzed the data, then proposed our hypothesis that the pathogenic gene of TDO syndrome DLX3 mutation regulates stemness maintenance and self-renewal ability of BMSCs through H19/FGF2/Oct4 axis. We are planning to investigate the underlying mechanism regarding DLX3 enhances stemness maintenance and self-renewal ability of BMSCs. Herein, China has stepped into an aging society, and bone health problem in the elder has been concerned by the whole society. Our research achievements will help to discover a new endogenous method for stemness maintenance of BMSCs; to figure out the pathogenesis of TDO syndrome on bone characterization aspect; to put forward a for treating and preventing osteoporosis and other bone metabolic diseases.