Multi-omics analysis to examine gene expression and metabolites from multisite adipose-derived mesenchymal stem cells

The aim of this study was to explore the gene expression and metabolites among multisite adipose-derived mesenchymal stem cells, and investigate the metabolic pathway of multisite adipose-derived mesenchymal stem cells using a multi-omics analysis. Subcutaneous adipose-derived mesenchymal stem cells (SASCs), perirenal adipose-derived mesenchymal stem cells (PASCs), and epididymal adipose-derived mesenchymal stem cells (EASCs) were isolated from Sprague Dawley rats. RNA and metabolites were extracted and sequenced using transcriptomics and metabolomics analyses, respectively. There were 720 differentially expressed genes (DEGs) in EASCs and 688 DEGs in PASCs compared with SASCs; there were 166 unique DEGs in EASCs, 134 unique DEGs in PASCs, and 554 common DEGs between EASCs and PASCs. Furthermore, there were 220 differential metabolites in EASCs, 249 differential metabolites in PASCs, 83 unique differential metabolites in EASCs, 112 unique differential metabolites in PASCs, and 137 common differential metabolites between EASCs and PASCs. The transcriptomics and metabolomics analyses identified four hub genes, one in EASCs and three in PASCs. There are functional differences among multisite adipose-derived mesenchymal stem cells that may be related to the hub genes Atac2, Rrm1, Rrm2, and Gla. The relevant signaling pathways are the Ras signaling pathway, HIF-1 signaling pathway, and the p53 signaling pathway.本研究旨在探究多部位来源的脂肪间充质干细胞（adipose-derived mesenchymal stem cells）的基因表达谱与代谢物特征，并通过多组学分析手段解析其代谢通路。本研究从斯普拉格-道利（Sprague Dawley）大鼠体内分离得到皮下脂肪间充质干细胞（subcutaneous adipose-derived mesenchymal stem cells, SASCs）、肾周脂肪间充质干细胞（perirenal adipose-derived mesenchymal stem cells, PASCs）以及附睾脂肪间充质干细胞（epididymal adipose-derived mesenchymal stem cells, EASCs）。分别通过转录组学与代谢组学分析完成RNA与代谢物的提取及测序。相较于SASCs，EASCs中存在720个差异表达基因（differentially expressed genes, DEGs），PASCs中存在688个差异表达基因；其中EASCs特有差异表达基因166个，PASCs特有差异表达基因134个，二者共有差异表达基因554个。此外，EASCs中存在220种差异代谢物，PASCs中存在249种差异代谢物；其中EASCs特有差异代谢物83种，PASCs特有差异代谢物112种，二者共有差异代谢物137种。转录组学与代谢组学分析共筛选得到4个核心基因（hub genes），其中EASCs中1个，PASCs中3个。多部位来源的脂肪间充质干细胞存在功能差异，该差异可能与核心基因Atac2、Rrm1、Rrm2及Gla相关。相关信号通路包括Ras信号通路、缺氧诱导因子-1（HIF-1）信号通路以及p53信号通路。