利用基因表达综合(GEO)数据库中的肥胖及正常体重的髋关节炎滑膜组织的单细胞核糖核酸(RNA)测序结果(GSE152815)，分析两者中细胞组成及功能的差异，探讨其代谢重编程及微环境稳态失衡的变化，以期为相关领域的研究者提供参考。

利用GEO数据库中的GSE152815数据，通过质控、无监督聚类、轨迹分析、基因富集分析、基因调控网络分析等方法，采用Wilcoxon秩和检验和Kruskal-Wallis秩和检验等确定基因表达差异之间的统计学意义。

通过质控、无监督聚类，并根据各个亚群的标志分子，可以将滑膜组织分为4群，分别为滑膜成纤维祖细胞(SFPCs)，滑膜肥大软骨细胞(SHTCs)，滑膜成纤维细胞(SFBs)和滑膜纤维软骨细胞(SFCs)。轨迹分析发现SFPCs可向SHTCs、SFBs及SFCs分化，在分化过程中，脂肪酸代谢相关的基因，载脂蛋白E(APOE)以及ATP结合盒转运体A1(ABCA1)等基因的表达量逐渐上升(Z ＝25.17、17.89，均为P<0.05)，而葡萄糖代谢的相关基因的表达量则逐渐下降(Z ＝15.32，P<0.05)。单细胞基因调控网络分析发现转录因子SOX4和MITF可以通过联合调控APOE和ABCA1等分子来调控细胞的脂肪酸代谢功能。

肥胖患者及正常体重患者的滑膜的微环境紊乱，可能会导致部分滑膜细胞的代谢紊乱，由原来的葡萄糖代谢重编程为脂肪酸代谢，而这可能与转录因子SRY盒转录因子4(SOX4)和小眼畸形转录因子(MITF)调控的APOE、ABCA1等基因密切相关。明确代谢重编程在这些细胞中的变化，有助于研究不同代谢重编程对细胞功能的影响，为研究骨关节炎等疾病的代谢重编程提供思路以及新途径。

To use the single-cell RNA sequencing results (GSE152815) of obese and normal-weight hip arthritis synovial tissues in gene expression omnibus(GEO) database to analyze the differences in cell composition and function between the two, and to explore their metabolic reprogramming and the imbalance of microenvironment homeostasis, in order to provide references for researchers in related fields.

Using the GSE152815 data in the GEO database, through quality control, unsupervised clustering, trajectory analysis, gene enrichment analysis, gene regulatory network analysis and other methods, Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used to determine the statistical significance of differences in gene expression.

Through quality control, unsupervised clustering, and according to the marker molecules of each subgroup, synovial tissue can be divided into four groups, namely synovial fibroblast progenitor cells (SFPCs), synovial hypertrophic chondrocytes (SHTCs), synovial fibroblast cells (SFBs) and synovial fibrochondrocytes (SFCs). Trajectory analysis found that SFPCs can differentiate into SFBs and SFCs. During the differentiation process, the expression of fatty acid metabolism-related genes-apolipoprotein E (APOE) and ATP binding cassette transporter A1 (ABCA1) gradually increase(Z =25.17, 17.89, both P<0.05), while the ability to metabolize glucose gradually declines(Z =15.32, P<0.05). Analysis of single-cell gene regulatory network found that transcription factors [SRY-box transcription factor 4(SOX4) and microphthalmia-associated transcription factor (MITF)] could regulate cell fatty acid metabolism by co-regulating molecules such as APOE and ABCA1.

The results confirmed that the microenvironment disorder of the synovial membrane of obese patients and normal-weight patients will cause the metabolic disorder of some synovial cells, reprogramming from the original glucose metabolism to fatty acid metabolism, which may be closely related to genes such as APOE and ABCA1 regulated by transcription factor SOX4 and MITF. Clarifying the changes of metabolic reprogramming in these cells will help to study the influence of different metabolic reprogramming on cell function, and provide ideas and new ways for studying metabolic reprogramming of osteoarthritis and other diseases.