动脉粥样硬化是衰老、营养、代谢、环境和精神等多因素所致复杂血管病变，最近许多研究发现干/祖细胞在血管内皮修复/再生和新生内膜形成中扮演重要角色，进而提出了血管损伤修复及重塑的新理论--干细胞假说，课题组通过大量前期研究证实血管外膜干/祖细胞是血管损伤性疾病病变发生及血管重塑中一个重要细胞来源并参与血管重塑的形成和进展，课题拟从以下三方面进行研究。第一：利用遗传谱系示踪，观察代谢失调如何影响血管外膜干/祖细胞参与血管重塑病理过程。第二：利用单细胞测序，观察脂质代谢异常小鼠及正常小鼠在血管损伤后其血管外膜及新生内膜发生的表型及组成变化。第三：观察代谢环境改变如何通过调控血管外膜干/祖细胞内在代谢重编程进而影响其向血管细胞定向分化及增殖迁移等过程中的功能角色及具体机制。本项目拓展了干/祖细胞在血管重塑中的研究，同时为干细胞药物调控和治疗开辟了新的思路。

Atherosclerosis is a complex disease caused by multiple factors including aging, nutrition, metabolism, environment and mental disorders. Recent studies have revealed an important role of stem/progenitor cells in the vascular remodeling, establishing a new stem cell hypothesis in vascular injury and regeneration. Previous studies from our group have confirmed that stem/progenitor cells, especially the adventitial stem/progenitor cells, are an important cell source for vascular remodeling. This study aims to explore the role of metabolic regulation of adventitial stem/progenitor cells in vascular remodeling, and the underlying mechanisms. Firstly, using a mouse model of cell lineage tracing, we will investigate on how metabolic disorders affect the adventitial stem/progenitor cells during vascular remodeling. Secondly, using single cell gene sequencing techniques, we will compare the phenotypic and compositional changes of different cell types within vascular adventitia and neointima in dyslipidemic and normal mice after vascular injury. Finally, we will focus on the effects of the alteration of extracellular metabolic microenvironment on cellular metabolic reprogramming and stem cell functions, including migration, proliferation and differentiation and further explore the possible intrinsic metabolic-related mechanisms involved in these processes. Thus, the current study could provide the basic information on the role of vascular stem cells in vascular remodeling, which could serve as a new cell target for the drug discovery and treatment of vascular diseases.