R-spondin2在人多能干细胞造血分化中的功能和作用机制研究

人多能干细胞可以分化为造血干/祖细胞和功能性血细胞。然而，现有的造血分化体系效率低，且不能够生成具有移植能力的造血干细胞，同时诱导分化产生的红细胞和血小板数量远低于临床所需输血标准。阐明人多能干细胞造血分化过程及调控机制有助于解决这些问题。我们前期研究发现R-spondin2显著促进生血内皮细胞和造血祖细胞的产生，提示R-spondin2可能在人多能干细胞造血分化过程中具有重要作用。本研究将进一步揭示R-spondin2在人多能胚胎干细胞造血分化的作用及其发挥作用的窗口期，同时探索其对成年造血的影响，并利用RNA-SEQ技术和CRISPR/Cas9技术阐明其作用机制，加深人们对人多能干细胞造血分化过程及调控机制的理解，为建立高效、高质造血分化体系提供理论依据。

Human pluripotent stem cells (hPSCs) can differentiate into hematopoietic stem/progenitor cells and functional blood cells. However, the efficiency of hematopoietic differentiation is low and the generation of RBCs and Platelets on a clinical scale and hematopoietic cells with robust and sustained multi-lineage engraftment have not been achieved. Elucidating the mechanism regulating hematopoietic differentiation from hPSCs is critical in solving these problems. Our preliminary data suggested that R-spondin2 promoted hemogenic endothelium and hematopoietic stem/progenitor cells development from hPSCs. These results indicated that R-spondin2 might play important roles in regulating the process of hPSCs differentiating into hematopoietic cells. In this study, we will dissect the stage-specific function of R-spondin2 in hPSCs hematopoiesis and its potential effect on definitive hematopoiesis. Furthermore, the potential downstream targets of R-spondin2 will be explored by using RNA-SEQ and CRISPR/Cas9 technology. Our results will clarify the function and molecular mechanisms of R-spondin2 in regulating hPSCs hematopoietic differentiation and it might facilitate the derivation of hematopoietic cells from hPSCs with high efficiency and quality.