微重力影响造血干细胞增殖和定向分化的分子网络及与机制

Space microgravity induces a series of adverse physiological reactions in astronauts, including the destruction of the hematopoietic system and the immune system and the degradation of tissues, such as bone loss and muscle atrophy. Hematopoietic stem cells possess a high degree of self-renewal ability, and can differentiate into red blood cells and immune cells, and play an important role in the homeostasis of hematopoietic system and immune system. Therefore, it is essential to carry out the study on the effects of microgravity on hematopoietic stem cell proliferation and differentiation as well as the relevant molecular mechanisms. On the basis of our recent related studies, we will mainly conduct the following studies in the present project: 1) The effects of space microgravity and simulated microgravity on the proliferation of hematopoietic stem cells; 2) The effects of space microgravity and simulated microgravity on the differentiation of hematopoietic stem cells into macrophages; 3) The molecular mechanisms involved in the effects of space microgravity and simulated microgravity on hematopoietic stem cell proliferation; 4) The molecular mechanisms related to the effects of space microgravity and simulated microgravity on hematopoietic stem cell differentiation into macrophages. We believe that this series of studies will deepen our understanding about the effects of microgravity on hematopoietic stem proliferation and differentiation, which provide an important theoretical basis for the prevention and treatment of the disorders caused by the space microgravity environment.

空间微重力环境导致宇航员产生一系列的生理/病理反应，包括造血/免疫系统的受损及骨骼和肌肉退化等。造血干细胞具有高度自我更新并发育分化为免疫细胞的能力，对造血/免疫系统维持具有重要作用。因此，非常有必要开展微重力环境对造血干细胞增殖和定向分化影响的实验研究。在我们前期工作基础上，本项目将应用组学、分子生物学、生化等技术，重点解析微重力调控造血干细胞增殖和定向分化为巨噬细胞的分子网络和重要分子机制，主要进行：1）空间微重力和模拟微重力对造血干细胞增殖的影响；2）空间微重力和模拟微重力对造血干细胞定向分化为巨噬细胞的影响；3）空间微重力和模拟微重力调控造血干细胞增殖的分子机制；4）空间微重力和模拟微重力调控造血干细胞定向分化为巨噬细胞的分子机制。该研究将明确微重力直接影响造血干细胞增殖和定向分化影响的特点，将加深我们对微重力影响造血干细胞的重要分子网络，为有效防治提供必要的理论基础与指导。

空间微重力环境导致宇航员产生一系列的生理/病理反应，包括造血/免疫系统的受损及骨.骼和肌肉退化等。造血干细胞具有高度自我更新并发育分化为免疫细胞的能力，对造血/免疫系统的维持具有重要作用。因此，非常有必要开展微重力环境对造血干细胞增殖和定向分化影响的实验研究。本项目中，我们阐明了微重力调控造血干/祖细胞增殖的规律和分子机制，证明空间微重力和模拟微重力均能通过下造血干/祖细胞中cKit‐Ras/cAMP‐CREB信号通路下调细胞增殖。本项目还进一步阐明了微重力调控造血干/祖细胞向巨噬细胞定向分化的规律和分子机制，证明空间微重力和模拟微重力通过下调巨噬细胞发育过程中的Ras/Erk/NFkB信号通路抑制造血干/祖细胞想巨噬细胞的定向分化，而且微重力能够抑制巨噬细胞M1型极化、促进M2极化。本项目研究成果能够为有效防治空间微重力引起的造血/免疫系统受损提供必要的理论基础与指导。