Transcriptional Dynamics and Key Regulators of Adipogenesis in Mouse Embryonic Stem Cells: Insights from Robust Rank Aggregation Analysis

Int J Mol Sci. 2024 Aug 23;25(17):9154. doi: 10.3390/ijms25179154.

Abstract

Embryonic stem cells are crucial for studying developmental biology due to their self-renewal and pluripotency capabilities. This research investigates the differentiation of mouse ESCs into adipocytes, offering insights into obesity and metabolic disorders. Using a monolayer differentiation approach over 30 days, lipid accumulation and adipogenic markers, such as Cebpb, Pparg, and Fabp4, confirmed successful differentiation. RNA sequencing revealed extensive transcriptional changes, with over 15,000 differentially expressed genes linked to transcription regulation, cell cycle, and DNA repair. This study utilized Robust Rank Aggregation to identify critical regulatory genes like PPARG, CEBPA, and EP300. Network analysis further highlighted Atf5, Ccnd1, and Nr4a1 as potential key players in adipogenesis and its mature state, validated through RT-PCR. While key adipogenic factors showed plateaued expression levels, suggesting early differentiation events, this study underscores the value of ESCs in modeling adipogenesis. These findings contribute to our understanding of adipocyte differentiation and have significant implications for therapeutic strategies targeting metabolic diseases.

Keywords: adipogenesis; embryonic stem cells; robust ranking aggregation; transcriptomics.

MeSH terms

  • Adipocytes* / cytology
  • Adipocytes* / metabolism
  • Adipogenesis* / genetics
  • Animals
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Differentiation* / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Mice
  • Mouse Embryonic Stem Cells* / cytology
  • Mouse Embryonic Stem Cells* / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Transcription, Genetic

Substances

  • PPAR gamma
  • CCAAT-Enhancer-Binding Proteins
  • Pparg protein, mouse
  • CEBPA protein, mouse