title: Brown-like adipose progenitors derived from human induced pluripotent stem cells: Identification of critical pathways governing their adipogenic capacity.
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.
authors: Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
authors: Anne-Laure
authors: AL
authors: Hafner
authors: Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
authors: Julian
authors: J
authors: Contet
authors: Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
authors: Christophe
authors: C
authors: Ravaud
authors: Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
authors: Xi
authors: X
authors: Yao
authors: Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
authors: Phi
authors: P
authors: Villageois
authors: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53715, USA.
authors: Kran
authors: K
authors: Suknuntha
authors: Inserm U910, Faculty of Medicine La Timone, Marseille, France.
authors: Karima
authors: K
authors: Annab
authors: Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
authors: Pascal
authors: P
authors: Peraldi
authors: Inserm U910, Faculty of Medicine La Timone, Marseille, France.
authors: Bernard
authors: B
authors: Binetruy
authors: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53715, USA.
authors: Igor I
authors: II
authors: Slukvin
authors: Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
authors: Annie
authors: A
authors: Ladoux
authors: Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
authors: Christian
authors: C
authors: Dani
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004149:Dioxoles / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D000072041:PAX3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000235:genetics / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D051017:Apoptosis Regulatory Proteins; D001205:Ascorbic Acid; D001549:Benzamides; D015415:Biomarkers; D004149:Dioxoles; D004815:Epidermal Growth Factor; D007453:Iodide Peroxidase; D000072041:PAX3 Transcription Factor; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D000097564:Iodothyronine Deiodinase Type II; C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; C502539:CIDEA protein, human; C489409:PAX3 protein, human; C492123:ZIC1 protein, human