Multi-Omics Analysis to Examine Gene Expression and Metabolites From Multisite Adipose-Derived Mesenchymal Stem Cells.

Chuanxi Yang,Wei Sun,Tingting Wu,Jing Shi,Kun Zhao,Xiangqing Kong,Xiaoguang Wu,Jing Zhang

doi:10.3389/fgene.2021.627347

Abstract

This study aimed at exploring the gene expression and metabolites among multisite adipose-derived mesenchymal stem cells (ASCs) and investigate the metabolic pathway 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 226 differential metabolites in EASCs, 255 differential metabolites in PASCs, 83 unique differential metabolites in EASCs, 112 unique differential metabolites in PASCs, and 143 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 ASCs 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. In conclusion, compared with SASCs, our multi-omics analysis identified that EASCs with higher Acat2 expression may be more correlated to fat metabolism and insulin resistance, while PASCs with abnormal expression of Rrm1/2 and Gla may be more correlated with some malignant tumors and cardiac-cerebral vascular disease.

Highlights

Obesity, which poses a grave threat to humankind, has become one of the most important chronic diseases
Using Metacore system, the top 10 different enrichments in pathway maps, Gene Ontology (GO) processes, and process networks of differentially expressed genes (DEGs) in epididymal adipose-derived mesenchymal stem cells (EASCs) and perirenal adipose-derived mesenchymal stem cells (PASCs) are shown in Supplementary Figures 1A,B
Gene Ontology (GO) process enrichment analyses show the common DEGs are most relevant to actin cytoskeleton organization, the PASCs are strongly associated with supramolecular fiber organization, and the EASCs are most enriched in the mitotic cell cycle

Summary

Introduction

Obesity, which poses a grave threat to humankind, has become one of the most important chronic diseases. As early as 1956, Vague (1956) proposed that obesity as an important risk factor for cardiovascular disease is related to the distribution of adipose tissue in the human body, not just the increase of total adipose tissue. Previous studies have shown that the expansion of SAT is dominated by adipocyte hyperplasia, while VAT [including omental, mesenteric, and perirenal adipose tissue (PAT)] is primarily increased by adipocyte hypertrophy (Joe et al, 2009). The accumulation of VAT is more closely associated with cardiovascular disease, insulin resistance, hypermetabolism, and cancer (Dobbelsteyn et al, 2001; Fox et al, 2007; Tran et al, 2008; Tchernof and Després, 2013; Silva and Baptista, 2019). Compared with other VATs [such as epididymal adipose tissue (EAT)], PAT has some characteristics of BAT. Some investigators indicate that EAT maximum thickness is better associated with cardiovascular risk factors (Kawamoto et al, 2002; Nishina et al, 2003)

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