Production of functional classical brown adipocytes from human pluripotent stem cells using specific hemopoietin cocktail without gene transfer.

Department of Disease Control, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.

Cell metabolism 2012 Sep 5

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Brown adipose tissue is attracting much attention due to its antiobestic effects; however, its development and involvement in metabolic improvement remain elusive. Here we established a method for a high-efficiency (>90%) differentiation of human pluripotent stem cells (hPSCs) into functional classical brown adipocytes (BAs) using specific hemopoietin cocktail (HC) without exogenous gene transfer. BAs were not generated without HC, and lack of a component of HC induced white adipocyte (WA) marker expressions. hPSC-derived BA (hPSCdBA) showed respiratory and thermogenic activation by β-adrenergic receptor (AdrRβ) stimuli and augmented lipid and glucose tolerance, whereas human multipotent stromal cell-derived WA (hMSCdWA) improved lipid but inhibited glucose metabolism. Cotransplantation of hPSCdBA normalized hMSCdWA-induced glucose intolerance. Surprisingly, hPSCdBAs expressed various hemopoietin genes, serving as stroma for myeloid progenitors. Moreover, AdrRβ stimuli enhanced recovery from chemotherapy-induced myelosuppression. Our study enhances our understanding of BA, identifying roles in metabolic and hemogenic regulation. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

Miwako Nishio, Takeshi Yoneshiro, Masako Nakahara, Shinnosuke Suzuki, Koichi Saeki, Mamoru Hasegawa, Yuko Kawai, Hidenori Akutsu, Akihiro Umezawa, Kazuki Yasuda, Kazuyuki Tobe, Akira Yuo, Kazuo Kubota, Masayuki Saito, Kumiko Saeki. Production of functional classical brown adipocytes from human pluripotent stem cells using specific hemopoietin cocktail without gene transfer. Cell metabolism. 2012 Sep 5;16(3):394-406