Functional human beige adipocytes from induced pluripotent stem cells

Anne Claire Guénantin, Nolwenn Briand, Emilie Capel, Florent Dumont, Romain Morichon, Claire Provost, Francesca Stillitano, Dorota Jeziorowska, Jean Pierre Siffroi, Roger J. Hajjar, Bruno Fève, Jean Sébastien Hulot, Philippe Collas, Jacqueline Capeau, Corinne Vigouroux

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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, ourmethod 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 hiPSCderived 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.

Original languageEnglish
Pages (from-to)1470-1478
Number of pages9
JournalDiabetes
Volume66
Issue number6
DOIs
StatePublished - 1 Jun 2017

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