Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte-like phenotypeReport as inadecuate




Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte-like phenotype - Download this document for free, or read online. Document in PDF available to download.

BMC Genomics

, 14:625

Transcriptomics

Abstract

BackgroundThe adipose tissue is an endocrine regulator and a risk factor for atherosclerosis and cardiovascular disease when by excessive accumulation induces obesity. Although the adipose tissue is also a reservoir for stem cells ASC their function and -stemcellness- has been questioned. Our aim was to investigate the mechanisms by which obesity affects subcutaneous white adipose tissue WAT stem cells.

ResultsTranscriptomics, in silico analysis, real-time polymerase chain reaction PCR and western blots were performed on isolated stem cells from subcutaneous abdominal WAT of morbidly obese patients ASCmo and of non-obese individuals ASCn. ASCmo and ASCn gene expression clustered separately from each other. ASCmo showed downregulation of -stemness- genes and upregulation of adipogenic and inflammatory genes with respect to ASCn. Moreover, the application of bioinformatics and Ingenuity Pathway Analysis IPA showed that the transcription factor Smad3 was tentatively affected in obese ASCmo. Validation of this target confirmed a significantly reduced Smad3 nuclear translocation in the isolated ASCmo.

ConclusionsThe transcriptomic profile of the stem cells reservoir in obese subcutaneous WAT is highly modified with significant changes in genes regulating stemcellness, lineage commitment and inflammation. In addition to body mass index, cardiovascular risk factor clustering further affect the ASC transcriptomic profile inducing loss of multipotency and, hence, capacity for tissue repair. In summary, the stem cells in the subcutaneous WAT niche of obese patients are already committed to adipocyte differentiation and show an upregulated inflammatory gene expression associated to their loss of stemcellness.

KeywordsHuman adipose-derived stem cells Subcutaneous adipose tissue Cardiovascular risk factors Transcriptome Inflammatory genes AbbreviationsASCAdipose-derived stem cells

ASCnASC derived from non-obese individuals

ASCmoASC derived from morbid obese patients

BMIBody mass index

CVRFCardiovascular risk factors

FDRFalse discovery rate

HDLHigh density lipoprotein cholesterol

LDLLow density lipoprotein cholesterol

MSCMesenchymal stem cells

PCAPrincipal component analysis

PCRPolymerase chain reaction

SVFStromal vascular fraction

WATWhite adipose tissue.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-14-625 contains supplementary material, which is available to authorized users.

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Author: Blanca Oñate - Gemma Vilahur - Sandra Camino-López - Alberto Díez-Caballero - Carlos Ballesta-López - Juan Ybarra - Fabr

Source: https://link.springer.com/







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