利用单细胞测序技术探讨miR-92a-3p对骨髓干细胞向软骨细胞分化过程影响的机制研究

组织工程软骨种子细胞成软骨分化后稳定性较差且早期易退变一直是限制其大规模推广应用到临床的难题，其本质问题主要在于细胞调控.申请人团队在实验过程中发现部分细胞与成软骨分化细胞整体趋势不同，不同的细胞亚群呈现出不同的分化趋势。申请人在上一个国自然基金资助下证实miR-92a-3p在hMSCs成软骨分化中特异性高表达，可同时促进成软骨分化及软骨退变，即具备双向调控能力。我们通过预实验发现，miR-92a-3p对各个细胞亚群所起到的作用也不相同，同时发现在成软骨分化过程中有无miR-92a-3p这一条件对于M基因的变化起着十分重要的作用并影响成软骨分化过程。本研究旨在通过细胞-组织-整体层面更好的阐述miR-92a-3p对于骨髓干细胞向软骨细胞分化过程中个各胞亚群的影响以及更精准的找到在其过程中miR-92a-3p影响的下游靶点，为解决软骨分化后稳定性较差且早期易退变的难题提供新思路。

The stability of seeded chondrogenic cells after chondrogenic differentiation is poor and early degeneration is always a difficult problem to limit its large-scale application in clinical practice.The essential problem lies in cell regulation.During the experiment, the applicant team found that the overall trend of some cells was different from that of chondroblast differentiated cells, and different cell subgroups showed different differentiation trends.Under the support of the previous national natural science foundation, the applicant confirmed that mir-92a-3p is highly expressed specifically in the chondrogenic differentiation of hMSCs, which can promote chondrogenic differentiation and cartilage degeneration at the same time, namely, it has two-way regulation ability.Through preliminary experiments, we found that mir-92a-3p also had different effects on each cell subgroup, and it was found that the presence or absence of mir-92a-3p in the chondrogenic differentiation process played a very important role in the change of M gene and affected the chondrogenic differentiation process.This study aims to better elucidation the effect of mir-92a-3p on each cell subgroup of bone marrow stem cells in the process of chondrogenic differentiation and to more accurately find the downstream target of the effect of mir-92a-3p in the process through the cell-tissue-whole level, providing a new idea to solve the problem of poor stability after chondrogenic differentiation and early degeneration.