title: MYC is an early response regulator of human adipogenesis in adipose stem cells.
abstract: Adipose stem cell (ASC) differentiation is necessary for the proper maintenance and function of adipose tissue. The procurement and characterization of multipotent ASCs has enabled investigation into the molecular determinants driving human adipogenesis. Here, the transcription factor MYC was identified as a significant regulator of ASC differentiation. Expression of MYC transcript and protein was found to accumulate during the initial course of differentiation. Loss-of-function analysis using siRNA mediated knockdown of MYC demonstrated inhibition of hormonally stimulated adipogenesis. MYC exhibited an early and sustained expression pattern that preceded down regulation of key suppressor genes, as well as induction of transcriptional and functional effectors. Glucocorticoid stimulation was identified as a necessary component for MYC induction and was found to impact adipogenesis in a concentration-dependent manner. Global gene expression analysis of MYC knockdown in ASC enriched for functional pathways related to cell adhesion, cytoskeletal remodeling, and transcriptional components of adipogenesis. These results identify a functional role for MYC in promotion of multipotent ASC to the adipogenic lineage.
authors.affiliation: The Hamner Institutes for Health Sciences, Institute for Chemical Safety Sciences, Research Triangle Park, North Carolina, United States of America.
authors.forename: Chad
authors.initials: C
authors.lastname: Deisenroth
authors.affiliation: The Hamner Institutes for Health Sciences, Institute for Chemical Safety Sciences, Research Triangle Park, North Carolina, United States of America.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Black
authors.affiliation: The Hamner Institutes for Health Sciences, Institute for Chemical Safety Sciences, Research Triangle Park, North Carolina, United States of America.
authors.forename: Salil
authors.initials: S
authors.lastname: Pendse
authors.affiliation: The Hamner Institutes for Health Sciences, Institute for Chemical Safety Sciences, Research Triangle Park, North Carolina, United States of America.
authors.forename: Linda
authors.initials: L
authors.lastname: Pluta
authors.affiliation: Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, North Carolina, United States of America.
authors.forename: Sam M
authors.initials: SM
authors.lastname: Witherspoon
authors.affiliation: The Hamner Institutes for Health Sciences, Institute for Chemical Safety Sciences, Research Triangle Park, North Carolina, United States of America.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: McMullen
authors.affiliation: The Hamner Institutes for Health Sciences, Institute for Chemical Safety Sciences, Research Triangle Park, North Carolina, United States of America.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Thomas
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: D016271:Proto-Oncogene Proteins c-myc