Brown-like adipose progenitors derived from human induced pluripotent stem cells: Identification of critical pathways governing their adipogenic capacity

Sci Rep. 2016 Aug 31;6:32490. doi: 10.1038/srep32490.

Abstract

Human induced pluripotent stem cells (hiPSCs) show great promise for obesity treatment as they represent an unlimited source of brown/brite adipose progenitors (BAPs). However, hiPSC-BAPs display a low adipogenic capacity compared to adult-BAPs when maintained in a traditional adipogenic cocktail. The reasons of this feature are unknown and hamper their use both in cell-based therapy and basic research. Here we show that treatment with TGFβ pathway inhibitor SB431542 together with ascorbic acid and EGF were required to promote hiPSCs-BAP differentiation at a level similar to adult-BAP differentiation. hiPSC-BAPs expressed the molecular identity of adult-UCP1 expressing cells (PAX3, CIDEA, DIO2) with both brown (ZIC1) and brite (CD137) adipocyte markers. Altogether, these data highlighted the critical role of TGFβ pathway in switching off hiPSC-brown adipogenesis and revealed novel factors to unlock their differentiation. As hiPSC-BAPs display similarities with adult-BAPs, it opens new opportunities to develop alternative strategies to counteract obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Brown / cytology
  • Adipocytes, Brown / drug effects
  • Adipocytes, Brown / metabolism*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Ascorbic Acid / pharmacology
  • Benzamides / pharmacology
  • Biomarkers / metabolism
  • Cell Differentiation / drug effects
  • Cell Line
  • Dioxoles / pharmacology
  • Epidermal Growth Factor / pharmacology
  • Gene Expression
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism*
  • Iodide Peroxidase / genetics
  • Iodide Peroxidase / metabolism
  • PAX3 Transcription Factor / genetics
  • PAX3 Transcription Factor / metabolism
  • Signal Transduction / genetics*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism

Substances

  • 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
  • Apoptosis Regulatory Proteins
  • Benzamides
  • Biomarkers
  • CIDEA protein, human
  • Dioxoles
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • ZIC1 protein, human
  • Epidermal Growth Factor
  • iodothyronine deiodinase type II
  • Iodide Peroxidase
  • Ascorbic Acid