title: 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.
authors.affiliation: Department of Emergency and Organ Transplantation, Section on Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
authors.forename: Sebastio
authors.initials: S
authors.lastname: Perrini
authors.forename: Romina
authors.initials: R
authors.lastname: Ficarella
authors.forename: Ernesto
authors.initials: E
authors.lastname: Picardi
authors.forename: Angelo
authors.initials: A
authors.lastname: Cignarelli
authors.forename: Maria
authors.initials: M
authors.lastname: Barbaro
authors.forename: Pasquale
authors.initials: P
authors.lastname: Nigro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peschechera
authors.forename: Orazio
authors.initials: O
authors.lastname: Palumbo
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.forename: Michele
authors.initials: M
authors.lastname: De Fazio
authors.forename: Annalisa
authors.initials: A
authors.lastname: Natalicchio
authors.forename: Luigi
authors.initials: L
authors.lastname: Laviola
authors.forename: Graziano
authors.initials: G
authors.lastname: Pesole
authors.forename: Francesco
authors.initials: F
authors.lastname: Giorgino
mesh_terms: D050156:Adipogenesis; D053687:Adult Stem Cells / Q000145:classification* / Q000166:cytology / Q000378:metabolism*; D000368:Aged; D002454:Cell Differentiation; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D006801:Humans; D050152:Intra-Abdominal Fat / Q000166:cytology* / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D008875:Middle Aged; D050151:Subcutaneous Fat / Q000166:cytology* / Q000378:metabolism
chemical_list: D016207:Cytokines