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
Oñate, Blanca (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Vilahur, Gemma (Institut d'Investigació Biomèdica Sant Pau)
Camino-López, Sandra (Institut d'Investigació Biomèdica Sant Pau)
Díez-Caballero, Alberto (Centro Médico Teknon (Barcelona))
Ballesta-López, Carlos (Centro laparoscópico Doctor Ballesta)
Ybarra, Juan (Resistencia a la Insulina SL (Barcelona))
Moscatiello, Fabrizio (Centro Médico Teknon (Barcelona))
Herrero, Javier (Centro Médico Teknon (Barcelona))
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Fecha:	2013
Resumen:	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. © 2013 Oñate et al. ; licensee BioMed Central Ltd.
Ayudas:	Ministerio de Ciencia e Innovación SAF2010/16549 Ministerio de Economía y Competitividad RD12/0042/0027
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Cardiovascular risk factors ; Human adipose-derived stem cells ; Inflammatory genes ; Subcutaneous adipose tissue ; Transcriptome
Publicado en:	BMC genomics, Vol. 14 Núm. 1 (16 2013) , p. 625, ISSN 1471-2164

DOI: 10.1186/1471-2164-14-625
PMID: 24040759

12 p, 717.2 KB

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