Cd24调控造血干细胞炎性衰老的机制研究

Hematopoietic stem cells (HSC) aging contributes to aging-associated hematological diseases such as anemia, leukemia and defective immunity. An aging hematopoiesis is associated with altered commitment to myeloid vs lymphoid lineages, with elevated numbers but functionally defective hematopoietic stem/ progenitor cells (HSPCs) and extramedullary hematopoiesis. Cytokines and intracellular regulators have been extensively reported as potential underlying mechanisms for hematopoietic aging, while a major hypothesis termed inflammaging (inflammatory response to tissue injuries contribute to the aging process) still need to be elucidated. Cd24 is a cell surface marker for multiple lineages of hematopoietic and non-hematopoietic cells, which function was reported as regulation of inflammatory response to intracellular components released after necrosis. Cd24 function in HSPC is unknown. Here we found that in comparison with young mice, old mice show reduced Cd24 level in bone marrow. We make hypothesis on that: Cd24 expression reduces in bone marrow during aging process, which cause increased cytokine. The increased cytokine accelerate hematopoietic aging process. Thus, we will use multiple approaches to study how Cd24 regulates hematopoietic stem cell aging and if Cd24 related to any hematopoietic aging disease process.

造血干细胞衰老会导致老年相关的许多造血系统疾病如贫血，白血病以及免疫系统缺陷等。造血系统的衰老呈现出一系列的表型如趋向于髓系细胞的分化，造血干细胞和前体细胞数目的增加但是功能减弱以及髓外造血的生成。目前已报道调控造血干细胞衰老的分子包括细胞内和细胞外因子，而细胞炎性因子促进衰老产生也是目前的主要假说。Cd24是一种细胞表面的标志物，其重要功能是能够抑制细胞损伤刺激的炎性因子释放，但Cd24在造血干细胞上的功能还不清楚。我们发现Cd24的表达在老年小鼠的骨髓中有所降低，于是我们提出假说：Cd24作为抑制炎症反应的膜蛋白，在老龄化过程中表达降低，导致炎性因子在组织中增加，进而造成小鼠造血干细胞老化的表型。因此，我们将用Cd24缺失型小鼠模型，流式细胞分选，骨髓移植，炎性因子检测等多种方法进行造血干细胞衰老的研究，阐明Cd24影响造血干细胞衰老的机制，为缓解造血系统老龄化提出新思路。