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ScRNA-seq from abdominal and gluteofemoral subcutaneous adipose tissue derived stem cells (ADSC)

ABSTRACT: Recent studies using single cell (sc) RNAseq, identified subpopulations of adipose derived stem cells (ADSCs) within the stroma vascular fraction of human adipose tissue, potentially leading to functionally distinct adipocyte populations. We aimed to extend this analysis by exploring the heterogeneity of the ADSCs within abdominal (ABD) vs gluteofemoral (GF) subcutaneous fat depots of apple and pear shaped pre-menopausal women. Using full-length SMART-seq scRNAseq technology and a panel of known stem cell and preadipocyte markers for identification, we detected 7 subpopulations of cells in both ABD and GF-ADSCs. Two ADSC subpopulations enriched the GF depot were characterized by increased expression of genes involved in cholesterol and fatty acid metabolism. Two subpopulations enriched in the ABD depot had gene expression signatures associated with inflammation and fibrosis. The body shape comparison revealed that apple-shaped women have a unique fibrotic ADSC subpopulation in their ABD depot and a high proportion of predicted highly proliferative preadipocytes in their GF depot. We propose that these depot and body shape specific ADSC populations could contribute to the metabolic complications associated with the differential fat distribution.

ORGANISM(S): Homo sapiens

PROVIDER: GSE209618 | GEO | 2025/07/11

REPOSITORIES: GEO

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Project description:Adipogenesis occurs through a specific gene program in undifferentiated fat progenitors. We hypothesized that the properties of the fat progenitors are regulated by hox genes, the developmental genes essential in different tissue stem cells. Their biased expression in white and brown fat implies roles in distinguishing the two fat types. Among 39 Hox genes, Hoxc8 is highly enriched in undifferentiated adipose tissue stem cells (ADSCs) and down-regulated in differentiated adipocytes. Forced expression of Hoxc8 suppressed adipocyte differentiation of ADSCs. Using microarrays, we investigated the effect of Hoxc8 overexpression on global transcripts in ADSCs. We compared among four groups: untreated ADSCs, adipogenic induction media (MDI)-treated ADSCs, MDI-treated ADSC-vector and MDI-treated ADSC-Hoxc8. A number of, but not all, adipogenesis-related genes are suppressed by Hoxc8. This dataset illustrates the global effect of Hoxc8, a developmental transcription factor, on the expression of adipogenesis-related genes. Gene expression was compared among untreated ADSCs (control), adipogenic induction media-treated ADSCs, adipogenic induction media-treated ADSC-vector (ADSCs transduced with control vector), and adipogenic induction media-treated ADSC-Hoxc8 (ADSCs transduced with human Hoxc8). Total RNA was isolated from ADSCs using the Qiagen RNeasy kit (Qiagen). At NimbleGen, quality and yield were verified before cDNA synthesis and Cy3-end labeling. The labeled cDNA samples were hybridized to Homo sapiens 4-Plex arrays (Roche NimbleGen, A4487001-00-01) that represent 24,000 human genes. Raw data files for each sample were normalized and background-corrected using a Robust Multi-Array Analysis as implemented by NimbleScan software. Students’ two-tail t-tests were conducted among the samples for each transcript and fold-change was determined. Transcripts whose abundance was significantly altered (P < 0.05) and an absolute fold change greater than 2 were defined as differentially regulated.

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ScRNA-seq from abdominal and gluteofemoral subcutaneous adipose tissue derived stem cells (ADSC)

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