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

Abstract

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. ASCSVF, ASCBottom, and ASCCeiling, 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 ASCSVF, ASCBottom and ASCCeiling from Sc fat were significantly different as compared to their homologous subsets of V-ASCs. Furthermore, ASCSVF, ASCCeiling and ASCBottom from the same fat depot were also distinct from each other. In this respect, both principal component analysis and hierarchical clusters analysis showed that ASCCeiling and ASCSVF shared a similar pattern of closely related genes, which was highly different when compared to that of ASCBottom. 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 ASCSVF, ASCBottom, and ASCCeiling 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, ASCCeiling and ASCBottom can be identified as two genetically and functionally heterogeneous ASC populations in addition to the ASCSVF, with ASCBottom 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.

Secretion of immunoregulatory cytokines by mesenchymal stem cells

“…Nevertheless, the published data demonstrating the secretion of IL-10 by MSCs are quite contradictory. Almost half of the papers discussed in the present review report positive secretion of IL-10 by MSCs [62,66,[81][82][83][84] , while the other half and our own experimental results reject such a possibility [60,64,69,78,[85][86][87][88] . It is quite logical to support the concept proposed by some authors claiming that MSCs secrete IL-10 under specific conditions with the inflammatory environment and presence of cytokines (IFNγ, IL-1b and TNFα) which activate certain Toll-like receptors on MSCs [63,65,67] .…”

“…Contrary to IL-10, there is no doubt that IL-6 is secreted by MSCs and almost all authors agree with this statement [69,78,82,84,86,87] . Its secretion by MSCs has been demonstrated both in mice and in humans [62,66] and is detected either after induction with TNFα, IL-1b and IFNγ or spontaneously [37,[61][62][63]72,95] .…”

2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue

“…For example, excess free fatty acid release from the omental adipose tissue interferes with liver metabolism and contributes to the development of hyperinsulinaemia and hypertriglyceridaemia. In addition, subcutaneous and omental adipose tissues are characterised by differences in the expression of genes and proteins related to glucose and lipid metabolism, lipid transport and cellular stress and inflammation (Linder et al 2004, Vohl et al 2004, Perez-Perez et al 2009, Peinado et al 2012, Montes-Nieto et al 2013, Perrini et al 2013.…”

Genetic analysis of the human hair roots as a tool for spaceflight experiments

“…PCA was used to demonstrate the homogeneity level of the transcriptional profiles of analyzed samples. In a PCA plot, samples with similar expression profiles are positioned in the proximity to each other [26,27]. The position of each sample was plotted against the X-, Y-, and Z-axes in a three-dimensional (3D) space (Figure 2), in which the closer distance of the samples to each other in 3D; therefore, the homology between samples is high.…”