脂肪干细胞成骨分化的潜在关键基因与信号通路

Potential key genes and signaling pathways of osteogenic differentiation of adipose-derived stem cells

目的探讨脂肪干细胞(ADSCs)成骨分化过程相关的关键基因和信号通路。方法从GEO数据库中下载GSE63754基因芯片数据,利用R语言的Limma软件包筛选出与ADSCs成骨分化过程相关的差异表达基因。针对差异表达基因构建蛋白质互相作用(PPI)网络和转录因子网络。通过cytoHubba插件筛选出与ADSCs成骨分化过程相关的潜在关键基因,采用R语言的clusterProfiler数据包对关键基因进行功能和通路富集分析。结果共筛选出556个差异表达基因,其中228个基因上调,228个基因下调。PPI网络共包含314个基因,共预测5个转录因子(ESRP1、PRKAA2、POU5F1B、ATF4HE和ZSCAN4)。cytoHubba筛选结果显示,LEP、IL1B、FGF2、CDH1、VEGFA、PPARG可能是ADSCs成骨分化过程相关的潜在关键基因;关键基因主要与p38丝裂原活化蛋白激酶(MAPK)通路相关,并可能与成骨细胞分化相关。结论LEP、IL1B、FGF2、CDH1、VEGFA、PPARG可能是ADSCs成骨分化过程相关的潜在关键基因,且p38 MAPK通路可能在这一过程中发挥重要作用。

Objective To explore the key genes and signaling pathways related to the osteogenic differentiation process of adipose-derived stem cells(ADSCs).Methods The GSE63754 microarray data were downloaded from the GEO database,and R package Limma was used to screen the differentially expressed genes(DEGs)related to the osteogenic differentiation process of ADSCs.The protein-protein interaction(PPI)network and transcription factor network were constructed targeting the DEGs.The potential key genes related to the osteogenic differentiation process of ADSCs were screened by cytoHubba plug-in,and function enrichment analysis and pathway enrichment analysis on the key genes were performed by using R package clusterProfiler.Results A total of 556 DEGs were identified,involving 228 up-regulated genes and 228 down-regulated genes.The PPI network included 314 genes and five transcription factors(ESRP1,PRKAA2,POU5F1B,ATF4HE and ZSCAN4)in total.cytoHubba screening results indicated that LEP,IL1B,FGF2,CDH1,VEGFA,and PPARG might be the potential key genes related to the osteogenic differentiation process of ADSCs;the key genes were commonly related to p38 mitogen-activated protein kinase(MAPK)pathway and might be related to osteoblast differentiation.Conclusion LEP,IL1B,FGF2,CDH1,VEGFA,and PPARG may be the potentially key genes related to the osteogenic differentiation process of ADSCs,and p38 MAPK pathway may play an important role in this process.