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

Autor: Juan Ybarra, Sandra Camino-López, Javier Herrero, Gemma Vilahur, Fabrizio Moscatiello, Lina Badimon, Blanca Oñate, Carlos Ballesta-López, A. Díez-Caballero
Rok vydání: 2013
Předmět:
Zdroj: BMC Genomics
Digital.CSIC. Repositorio Institucional del CSIC
instname
BMC GENOMICS
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
ISSN: 1471-2164
DOI: 10.1186/1471-2164-14-625
Popis: 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.
Acknowledgments This work was supported by Grants SAF 2010/16549, Retic-RIC (RD12/0042/0027) and Retic-TERCEL RD/06/0010/0017 from Instituto Salud Carlos III, Madrid, Spain; and Fundación Jesús Serra, Barcelona, Spain. L. B. is the Cardiovascular Research Chair, UAB, Barcelona, Spain. B. O. is the recipient of a Predoctoral Fellowship from Instituto Salud Carlos III, Madrid, Spain. G. V. is a recipient of a contract from the Innovation and Science Spanish Ministry (RyC-2009-5495), MICINN, Spain. The authors thank Marta Sánchez for her technical support
Databáze: OpenAIRE
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