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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.

SUBMITTER: Deisenroth C

PROVIDER: S-EPMC4250176 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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MYC is an early response regulator of human adipogenesis in adipose stem cells.

Deisenroth Chad C Black Michael B MB Pendse Salil S Pluta Linda L Witherspoon Sam M SM McMullen Patrick D PD Thomas Russell S RS

PloS one 20141201 12

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 s ...[more]

PMID: 25437437

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Project description:BackgroundObesity is characterized as a disease that directly affects the whole-body metabolism and is associated with excess fat mass and several related comorbidities. Dynamics of adipocyte hypertrophy and hyperplasia play an important role in health and disease, especially in obesity. Human adipose-derived stem cells (hASC) represent an important source for understanding the entire adipogenic differentiation process. However, little is known about the triggering step of adipogenesis in hASC. Here, we performed a proteogenomic approach for understanding the protein abundance alterations during the initiation of the adipogenic differentiation process.MethodshASC were isolated from adipose tissue of three donors and were then characterized and expanded. Cells were cultured for 24 hours in adipogenic differentiation medium followed by protein extraction. We used shotgun proteomics to compare the proteomic profile of 24 h-adipogenic, differentiated, and undifferentiated hASC. We also used our previous next-generation sequencing data (RNA-seq) of the total and polysomal mRNA fractions of hASC to study posttranscriptional regulation during the initial steps of adipogenesis.ResultsWe identified 3420 proteins out of 48,336 peptides, of which 92 proteins were exclusively identified in undifferentiated hASC and 53 proteins were exclusively found in 24 h-differentiated cells. Using a stringent criterion, we identified 33 differentially abundant proteins when comparing 24 h-differentiated and undifferentiated hASC (14 upregulated and 19 downregulated, respectively). Among the upregulated proteins, we shortlisted several adipogenesis-related proteins. A combined analysis of the proteome and the transcriptome allowed the identification of positive correlation coefficients between proteins and mRNAs.ConclusionsThese results demonstrate a specific proteome profile related to adipogenesis at the beginning (24 hours) of the differentiation process in hASC, which advances the understanding of human adipogenesis and obesity. Adipogenic differentiation is finely regulated at the transcriptional, posttranscriptional, and posttranslational levels.

Dataset Information

MYC is an early response regulator of human adipogenesis in adipose stem cells.

Publications

MYC is an early response regulator of human adipogenesis in adipose stem cells.

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