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Diabetes. 2017 Jun;66(6):1470-1478. doi: 10.2337/db16-1107. Epub 2017 Mar 7.

Functional Human Beige Adipocytes From Induced Pluripotent Stem Cells.

Author information

1
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.
2
Metabolic Research Laboratories, Addenbrooke's Treatment Centre, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K.
3
Sorbonne Universités, Université Pierre et Marie Curie, INSERM UMR_S938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition, Paris, France.
4
Institut Cochin, Université Paris Descartes, INSERM U1016, Paris, France.
5
Plateforme LIMP, UMS28 Phénotypage du petit animal, Université Pierre et Marie Curie, Paris, France.
6
Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY.
7
Sorbonne Universités, Université Pierre et Marie Curie, UMR_S1166, Institute of Cardiometabolism and Nutrition, France.
8
Sorbonne Universités, Université Pierre et Marie Curie, Assistance Publique-Hôspitaux de Paris, Service de Génétique et d'Embryologie Médicales, Hôpital Trousseau, Paris, France.
9
Assistance Publique-Hôspitaux de Paris, Service d'Endocrinologie, Hôpital Saint-Antoine, Paris, France.
10
Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
11
Norwegian Center for Stem Cell Research, Oslo University Hospital, Oslo, Norway.
12
Assistance Publique-Hôspitaux de Paris, Laboratoire Commun de Biologie et Génétique Moléculaires, Hôpital Saint-Antoine, Paris, France.

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.

PMID:
28270520
PMCID:
PMC5440013
DOI:
10.2337/db16-1107
[Indexed for MEDLINE]
Free PMC Article

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