Abstract
Objective. To characterize changes in gene expression profile during human mature adipocyte dedifferentiation in ceiling culture. Methods. Subcutaneous (SC) and omental (OM) adipose tissue samples were obtained from 4 participants paired for age and BMI. Isolated adipocytes were dedifferentiated in ceiling culture. Gene expression analysis at days 0, 4, 7, and 12 of the cultures was performed using Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to similarity of expression changes was used to identify overrepresented functions. Results. Four clusters gathered genes with similar expression between day 4 to day 7 but decreasing expression from day 7 to day 12. Most of these genes coded for proteins involved in adipocyte functions (LIPE, PLIN1, DGAT2, PNPLA2, ADIPOQ, CEBPA, LPL, FABP4, SCD, INSR, and LEP). Expression of several genes coding for proteins implicated in cellular proliferation and growth or cell cycle increased significantly from day 7 to day 12 (WNT5A, KITLG, and FGF5). Genes coding for extracellular matrix proteins were differentially expressed between days 0, 4, 7, and 12 (COL1A1, COL1A2, and COL6A3, MMP1, and TGFB1). Conclusion. Dedifferentiation is associated with downregulation of transcripts encoding proteins involved in mature adipocyte functions and upregulation of genes involved in matrix remodeling, cellular development, and cell cycle.
Highlights
The process of preadipocyte differentiation was viewed as an irreversible and terminal event leading to the formation of mature adipocytes
We demonstrated that expression of genes encoding proteins implicated in extracellular matrix (ECM) remodeling including matrixmetalloproteinase 1 (MMP1), fibroblast activated-protein (FAP), dipeptidyl peptidase IV (DPP4), and transforming growth factor β1 (TGFβ1) was significantly upregulated during the dedifferentiation process [2]
We first demonstrated an important difference in transcriptomic profile of adipocytes and dedifferentiated fat cells
Summary
The process of preadipocyte differentiation was viewed as an irreversible and terminal event leading to the formation of mature adipocytes. In vitro studies have shown that mature adipocytes are able to return to a more primitive phenotype when they are subjected to ceiling culture [1]. We have shown that the dedifferentiation process is relatively independent of the fat depot, obesity level, sex, or age of the cell donor [2]. Dedifferentiated fat (DFAT) cells express embryonic stem cell markers in addition to being multipotent. Ceiling culture represents an interesting model to study adipocyte biology and its role in metabolic homeostasis, especially the process of adipocyte dedifferentiation [6]
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