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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipocytes, Brown / cytology
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Adipocytes, Brown / drug effects
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Adipocytes, Brown / metabolism*
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Ascorbic Acid / pharmacology
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Benzamides / pharmacology
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Biomarkers / metabolism
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Cell Differentiation / drug effects
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Cell Line
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Dioxoles / pharmacology
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Epidermal Growth Factor / pharmacology
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Gene Expression
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Humans
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Induced Pluripotent Stem Cells / cytology
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Induced Pluripotent Stem Cells / drug effects
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Induced Pluripotent Stem Cells / metabolism*
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Iodide Peroxidase / genetics
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Iodide Peroxidase / metabolism
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Iodothyronine Deiodinase Type II
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PAX3 Transcription Factor / genetics
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PAX3 Transcription Factor / metabolism
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Signal Transduction / genetics*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transforming Growth Factor beta / antagonists & inhibitors*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism
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Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics
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Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism
Substances
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4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
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Apoptosis Regulatory Proteins
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Benzamides
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Biomarkers
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CIDEA protein, human
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Dioxoles
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PAX3 Transcription Factor
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PAX3 protein, human
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Transcription Factors
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Transforming Growth Factor beta
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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ZIC1 protein, human
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Epidermal Growth Factor
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Iodide Peroxidase
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Ascorbic Acid