Differences in Gene Expression and Cytokine Release Profiles Highlight the Heterogeneity of Distinct Subsets of Adipose Tissue-Derived Stem Cells in the Subcutaneous and Visceral Adipose Tissue in Humans

Differences in the inherent properties of adipose tissue-derived stem cells (ASC) may contribute to the biological specificity of the subcutaneous (Sc) and visceral (V) adipose tissue depots. In this study, three distinct subpopulations of ASC, i.e. ASC(SVF), ASC(Bottom), and ASC(Ceiling), were isolated from Sc and V fat biopsies of non-obese subjects, and their gene expression and functional characteristics were investigated. Genome-wide mRNA expression profiles of ASC(SVF), ASC(Bottom) and ASC(Ceiling) from Sc fat were significantly different as compared to their homologous subsets of V-ASCs. Furthermore, ASC(SVF), ASC(Ceiling) and ASC(Bottom) from the same fat depot were also distinct from each other. In this respect, both principal component analysis and hierarchical clusters analysis showed that ASC(Ceiling) and ASC(SVF) shared a similar pattern of closely related genes, which was highly different when compared to that of ASC(Bottom). However, larger variations in gene expression were found in inter-depot than in intra-depot comparisons. The analysis of connectivity of genes differently expressed in each ASC subset demonstrated that, although there was some overlap, there was also a clear distinction between each Sc-ASC and their corresponding V-ASC subsets, and among ASC(SVF), ASC(Bottom), and ASC(Ceiling) of Sc or V fat depots in regard to networks associated with regulation of cell cycle, cell organization and development, inflammation and metabolic responses. Finally, the release of several cytokines and growth factors in the ASC cultured medium also showed both inter- and intra-depot differences. Thus, ASC(Ceiling) and ASC(Bottom) can be identified as two genetically and functionally heterogeneous ASC populations in addition to the ASC(SVF), with ASC(Bottom) showing the highest degree of unmatched gene expression. On the other hand, inter-depot seem to prevail over intra-depot differences in the ASC gene expression assets and network functions, contributing to the high degree of specificity of Sc and V adipose tissue in humans.