title: Obesity short-circuits stemness gene network in human adipose multipotent stem cells.
abstract: The discovery of adipose multipotent stem cells has provided new insights to explore cellular mechanisms involved in adipose tissue function. In the present work, we aimed to evaluate how the adipogenic environment influences the stemness of the resident multipotent stem cells. To achieve this goal, human omental multipotent stem cells (hO-MSCs) were isolated, expanded, and characterized in both healthy lean and morbidly obese individuals. We observed decreased cell proliferation, premature senescence, and increased cytokine secretion associated with increasing body mass index of the patients. Consistent with the latter finding, the hO-MSCs derived from patients with morbid obesity lose their multilineage differentiation capacity associated with a dysregulation in the Wnt, Notch, and Sonic Hedgehog signaling pathways. Moreover, microRNAs involved in the regulation of stemness, cell differentiation, and senescence were also up-regulated in obese individuals. Altogether, our data show that obesity causes a general short circuit in the stemness gene network of hO-MSCs.
authors.affiliation: Fundacion Instituto Mediterráneo para el Avance de la Biotecnología y la Investigación Sanitaria (IMABIS), Malaga, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Roldan
authors.forename: Manuel
authors.initials: M
authors.lastname: Macias-Gonzalez
authors.forename: Regina
authors.initials: R
authors.lastname: Garcia
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Tinahones
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D000328:Adult; D002454:Cell Differentiation; D049109:Cell Proliferation; D016922:Cellular Senescence; D020219:Chondrogenesis; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D053823:Hedgehog Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000378:metabolism*; D009767:Obesity, Morbid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D051880:Receptors, Notch / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013851:Thinness / Q000235:genetics; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; D053823:Hedgehog Proteins; D035683:MicroRNAs; D051880:Receptors, Notch; C509239:SHH protein, human