Twist-1是中胚层发育必需的重要转录因子，但在正常造血中的作用尚无报道。我们在进行上一个国家自然基金课题时首次发现Twist-1参与正常造血干细胞（HSC）的维持及调控。进一步的预实验证据显示Twist-1可能与HSC衰老密切相关。本课题在前期发现的基础上，拟利用Twist-1条件敲除鼠模型，通过如下研究阐明Twist-1在HSC衰老中的作用及作用机制：1.检测敲除鼠稳态、移植后及应激损伤状态下造血系统以及HSC表型、功能、衰老相关标志及衰老相关基因、通路变化；2. 了解Twist-1敲除对小鼠造血系统应激损伤耐受力的影响；3. 找出介导Twist-1作用的已知衰老相关基因、通路，发现并鉴定新的衰老相关基因。对上述问题的探索，将有助于揭示HSC衰老的调控机制，对预防和治疗因HSC衰老引发的疾病有重要的理论意义和应用前景。

Transcription factor Twist-1 plays essential roles in specification and differentiation of mesoderm-derived tissues. However, the role of Twist-1 in hematopoietic stem cell (HSC) remains largely uncharacterized. While carrying out the project supported by the last National Natural Science Foundation of China, we found that that Twist-1 was involved in the regulation of normal HSC functional activity. Further evidence indicates that Twist-1 may function as an inhibitor of HSC senescence. By using Twist-1 conditional knockout mice, we plan to conduct the following investigations to elucidate the role of Twist-1 in HSC aging and its mechanism. 1. Examinate the phenotype, functional activity, markers and related genes of aging in hematopoietic system and HSC under steady state, after transplantation and undergone stress, respectively; 2. Evaluate the impact of Twist-1 knockout on the resistance of hematopoietic system to replicative and oxidative stress; 3. Investigate the genes and pathways mediated the function of Twist-1 in HSC senescence. The accomplishment of this project may provide new clues for elucidating the mechanism underlying the regulation of HSC aging, and lay a foundation for finding efficacious prophylaxis and therapy for aging-related diseases.