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Expansion and Adipogenesis Induction of Adipocyte Progenitors from Perivascular Adipose Tissue Isolated by Magnetic Activated Cell Sorting
Published on: June 30, 2017
POU2AF1 promotes MSCs adipogenesis by inhibiting HDAC1 expression
Yaqing Wang1, Luyang Wang2, Zhongping Su3
1Department of Cardiology, Geriatric Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Abstract:
Excessive production of visceral adipose is a major risk factor of many diseases. Inhibiting the adipogenesis of mesenchymal stem cells (MSCs) will be an efficient way to block adipose production. We illuminated POU class 2 homeobox associating factor 1 (POU2AF1) may promote MSCs adipogenesis by histone deacetylases 1 (HDAC1) signalling. Human retroperitoneal adipose-derived mesenchymal stem cells were isolated from overweight and control groups of patients. IncRNA microarray was used to identified gene expression levels. Adenovirus transduction and cellular small-interfering RNA transfection were used to achieve overexpression and interference of POU2AF1 or HDAC1. Adipogenesis was identified by Oil-red O staining, triglycende, cholesterol assay, real-time PCR and Western Blot. POU2AF1 expression was upregulated in retroperitoneal adipose tissue of overweight patients, and increased during adipogenesis. Overexpression of POU2AF1 promoted spontaneous adipogenesis without adipogenic treatment. Silencing of endogenous POU2AF1 in MSCs inhibited adipogenesis. Overexpression of POU2AF1 alleviated the translocation of HDAC1 to the nucleus. The mRNA level of HDAC1 was also reduced. Co-transfection of Ad-POU2AF1 and Ad-HDAC1 partially reversed the promotion effect of POU2AF1 overexpression in MSCs spontaneous adipogenic differentiation. POU2AF1 involves in the natural differentiation of human mesenchymal stem cells. Overexpression or silencing POU2AF1 could effectively induce or inhibit the adipogenesis by HDAC1 signaling.
Insights
POU class 2 homeobox associating factor 1 (POU2AF1) promotes mesenchymal stem cell (MSC) adipogenesis via histone deacetylases 1 (HDAC1) signaling. Modulating POU2AF1 effectively controls adipose production, offering therapeutic potential for metabolic diseases.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Excess visceral adipose tissue is a significant risk factor for numerous diseases.
- Inhibiting adipogenesis in mesenchymal stem cells (MSCs) is a key strategy to reduce adipose tissue accumulation.
- The role of POU class 2 homeobox associating factor 1 (POU2AF1) in MSC adipogenesis requires further elucidation.
Purpose of the Study:
- To investigate the role of POU2AF1 in the adipogenesis of human adipose-derived MSCs.
- To explore the underlying signaling pathway involving histone deacetylases 1 (HDAC1).
- To assess the potential of POU2AF1 as a therapeutic target for managing obesity and related diseases.
Main Methods:
- Isolation of human retroperitoneal adipose-derived MSCs from overweight and control patients.
- Gene expression analysis using IncRNA microarray.
- Manipulation of POU2AF1 and HDAC1 levels via adenovirus transduction and small-interfering RNA.
- Assessment of adipogenesis using Oil-red O staining, triglyceride and cholesterol assays, real-time PCR, and Western Blot.
Main Results:
- POU2AF1 expression was elevated in overweight patients' adipose tissue and increased during adipogenesis.
- POU2AF1 overexpression promoted MSC adipogenesis, while its silencing inhibited it.
- POU2AF1 overexpression reduced nuclear translocation and mRNA levels of HDAC1.
- Co-transfection with HDAC1 partially reversed POU2AF1's pro-adipogenic effects.
Conclusions:
- POU2AF1 plays a crucial role in human MSC adipogenesis through HDAC1 signaling.
- Modulating POU2AF1 expression offers a potential strategy to control adipose tissue development.
- Targeting POU2AF1 may provide a novel therapeutic approach for metabolic disorders associated with excessive adipose tissue.
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