title: Functional Human Beige Adipocytes From Induced Pluripotent Stem Cells.
abstract: Activation of thermogenic beige adipocytes has recently emerged as a promising therapeutic target in obesity and diabetes. Relevant human models for beige adipocyte differentiation are essential to implement such therapeutic strategies. We report a straightforward and efficient protocol to generate functional human beige adipocytes from human induced pluripotent stem cells (hiPSCs). Without overexpression of exogenous adipogenic genes, our method recapitulates an adipogenic developmental pathway through successive mesodermal and adipogenic progenitor stages. hiPSC-derived adipocytes are insulin sensitive and display beige-specific markers and functional properties, including upregulation of thermogenic genes, increased mitochondrial content, and increased oxygen consumption upon activation with cAMP analogs. Engraftment of hiPSC-derived adipocytes in mice produces well-organized and vascularized adipose tissue, capable of β-adrenergic-responsive glucose uptake. Our model of human beige adipocyte development provides a new and scalable tool for disease modeling and therapeutic screening.
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, INSERM UMR_S938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition, Paris, France anne-claire.guenantin@inserm.fr nolwenn.briand@inserm.fr.|Metabolic Research Laboratories, Addenbrooke's Treatment Centre, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Guénantin
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, INSERM UMR_S938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition, Paris, France anne-claire.guenantin@inserm.fr nolwenn.briand@inserm.fr.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Briand
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, INSERM UMR_S938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Capel
authors.affiliation: Institut Cochin, Université Paris Descartes, INSERM U1016, Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Dumont
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, INSERM UMR_S938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Morichon
authors.affiliation: Plateforme LIMP, UMS28 Phénotypage du petit animal, Université Pierre et Marie Curie, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Provost
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Francesca
authors.initials: F
authors.lastname: Stillitano
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, UMR_S1166, Institute of Cardiometabolism and Nutrition, France.
authors.forename: Dorota
authors.initials: D
authors.lastname: Jeziorowska
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Assistance Publique-Hôspitaux de Paris, Service de Génétique et d'Embryologie Médicales, Hôpital Trousseau, Paris, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Siffroi
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, INSERM UMR_S938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition, Paris, France.|Assistance Publique-Hôspitaux de Paris, Service d'Endocrinologie, Hôpital Saint-Antoine, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fève
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY.|Sorbonne Universités, Université Pierre et Marie Curie, UMR_S1166, Institute of Cardiometabolism and Nutrition, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.|Norwegian Center for Stem Cell Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Philippe
authors.initials: P
authors.lastname: Collas
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, INSERM UMR_S938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, INSERM UMR_S938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition, Paris, France.|Assistance Publique-Hôspitaux de Paris, Service d'Endocrinologie, Hôpital Saint-Antoine, Paris, France.|Assistance Publique-Hôspitaux de Paris, Laboratoire Commun de Biologie et Génétique Moléculaires, Hôpital Saint-Antoine, Paris, France.
authors.forename: Corinne
authors.identifier: 0000-0002-8181-4721
authors.initials: C
authors.lastname: Vigouroux
mesh_terms: D000069797:Adipocytes, Beige / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation; D050156:Adipogenesis; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D017690:Cell Transplantation; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D019788:Fluorodeoxyglucose F18; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007333:Insulin Resistance; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009765:Obesity; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000378:metabolism; D019275:Radiopharmaceuticals; D060888:Real-Time Polymerase Chain Reaction; D022722:Thermogenesis / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D007545:Isoproterenol