title: 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.
abstract: BACKGROUND
  The 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.
  
  
  RESULTS
  Transcriptomics, 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain. lbadimon@csic-iccc.org.
authors.forename: Blanca
authors.initials: B
authors.lastname: Oñate
authors.forename: Gemma
authors.initials: G
authors.lastname: Vilahur
authors.forename: Sandra
authors.initials: S
authors.lastname: Camino-López
authors.forename: Alberto
authors.initials: A
authors.lastname: Díez-Caballero
authors.forename: Carlos
authors.initials: C
authors.lastname: Ballesta-López
authors.forename: Juan
authors.initials: J
authors.lastname: Ybarra
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Moscatiello
authors.forename: Javier
authors.initials: J
authors.lastname: Herrero
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology*; D000328:Adult; D002318:Cardiovascular Diseases / Q000235:genetics; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006801:Humans; D009767:Obesity, Morbid / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012307:Risk Factors; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000166:cytology*; D049490:Systems Biology; D059467:Transcriptome
chemical_list: C497790:SMAD3 protein, human; D051900:Smad3 Protein
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