Identification of key genes of human bone marrow stromal cells adipogenesis at an early stage

Abstract

Background Bone marrow adipocyte (BMA), closely associated with bone degeneration, shares common progenitors with osteoblastic lineage. However, the intrinsic mechanism of cells fate commitment between BMA and osteogenic lineage remains unclear. Methods Gene Expression Omnibus (GEO) dataset GSE107789 publicly available was downloaded and analyzed. Differentially expressed genes (DEGs) were analyzed using GEO2R. Functional and pathway enrichment analyses of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were conducted by The Database for Annotation, Visualization and Integrated Discovery and Gene set enrichment analysis software. Protein–protein interactions (PPI) network was obtained using STRING database, visualized and clustered by Cytoscape software. Transcriptional levels of key genes were verified by real-time quantitative PCR in vitro in Bone marrow stromal cells (BMSCs) undergoing adipogenic differentiation at day 7 and in vivo in ovariectomized mice model. Results A total of 2,869 DEGs, including 1,357 up-regulated and 1,512 down-regulated ones, were screened out from transcriptional profile of human BMSCs undergoing adipogenic induction at day 7 vs. day 0. Functional and pathway enrichment analysis, combined with modules analysis of PPI network, highlighted ACSL1, sphingosine 1-phosphate receptors 3 (S1PR3), ZBTB16 and glypican 3 as key genes up-regulated at the early stage of BMSCs adipogenic differentiation. Furthermore, up-regulated mRNA expression levels of ACSL1, S1PR3 and ZBTB16 were confirmed both in vitro and in vivo. Conclusion ACSL1, S1PR3 and ZBTB16 may play crucial roles in early regulation of BMSCs adipogenic differentiation

Glucuronic acid metabolites of phenolic acids target AKT-PH domain to improve glucose metabolism

“…Then, the first 10 related pathways and 16 interacting proteins were analyzed through Kyoto Encyclopedia of Genes and Genomes (KEGG) ( https://bioinfo.capitalbio.com ) and String 9.1 ( https://www.string-db.org/ ). The protein–protein interaction network analysis was visualized using Cytoscape (version 3.7.1) ( Chen et al, 2020 ).…”

Alternative Methods as Tools for Obesity Research: In Vitro and In Silico Approaches

“…Importantly, such analyses allowed us to identify genes whose role in adipogenesis was previously unknown, such as ACSL1, S1PR3, ZBTB16, and GPC3. These may be closely associated with early-stage adipogenesis [ 64 , 65 ].…”

“…In silico analyses are also interesting in identifying potential key genes involved in the regulation of adipogenic differentiation. Genes/proteins enriched in adipogenesis pathways have been shown to participate in the in vitro differentiation process of different cell types, including MSCs [ 65 ]. Moreover, as adipogenesis is a fundamental process for fat metabolism, it is urgent to develop an approach to support clinical management and avoid complications related to metabolic imbalance, as in the case of obesity.…”