造血微环境中骨相关Sca1+细胞的发育及功能研究

造血微环境(Niche)调控造血干细胞(HSCs)的分化和自我更新。虽然Niche的构建过程逐渐明晰，但Niche各构建细胞的发育并未完全阐明，而且 Niche对HSCs分化的调控也有待研究。项目组已证实骨相关Sca1+细胞、CD146+细胞和CD166+细胞是Niche的构建细胞，Sca1+细胞是后两者的前体，但并不完全清楚这三群细胞之间的发育关系，以及它们对造血各系分化的影响。最近项目组观察到CD146+细胞可能是CD166+细胞的前体，DKK1基因可能调控Sca1+细胞的发育，而且Sca1+细胞可促进HSCs向巨噬细胞、树突状细胞分化。本项目拟在此基础上，验证CD146+细胞到CD166+细胞的发育过程，研究DKK1基因对Sca1+细胞发育的调控，解析Sca1+、CD146+和CD166+三种细胞调控HSCs分化的作用，为最终阐明Niche中Sca1+细胞发育机理及功能奠定基础。

Niche provides an essential microenvironment for maintaining hematopoietic stem cells (HSCs) self-renewing and differentiation. Although many studies have investigated the cellular compositions of hematopoietic niche, the development and the function of cellular compositions of the HSC niche are not well understood. Previously our group identified bone disassociated Sca1+cells, CD146+cells and CD166+cells acted as novel members of niche. Although Sca1+cells could differentiate into CD146+cells and CD166+cells, the accurate relationship among them and their effect on the differentiation of HSCs need to be further studied. Our previous studies indicated that CD146+cells might be the progenitors of CD166+cells and DKK1gene could be involved in the development of Sca1+cells. Moreover, we found Sca1+ cells induced HSCs to macrophages or dendritic cells. The current project will target on Sca1+, CD146+ and CD166+ cells to learn the development progress, the effect of DKK1 gene on their differentiation, as well as their function on the differentiation of HSC into myeloid cells. This study will have a significant contribution to the development of the cellular compositions of hematopoietic niche, and will provide new scenario for the interaction between niche and HSCs in normal physiological status, which is significant to prevention or therapy of hematological malignancies.