Production of Functional Classical Brown Adipocytes from Human Pluripotent Stem Cells using Specific Hemopoietin Cocktail without Gene
Cell Metabolism, Volume 16, Issue 3, 394-406, 5 September 2012
Copyright 2012 Elsevier Inc. All rights reserved.
10.1016/j.cmet.2012.08.001
VEGF, SCF, Flt3-L, and IL6 play roles in brown adipocyte (BA) differentiation
Human pluripotent stem cell (hPSC)-derived BAs improve lipid, glucose metabolism
hPSC-derived BAs serve as stroma for myeloid progenitor cells
ß-adrenergic receptor signaling promotes recovery from myelosuppression
Summary
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 ß-adrenergic receptor (AdrRß) 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, AdrRß stimuli enhanced recovery from chemotherapy-induced myelosuppression. Our study enhances our understanding of BA, identifying roles in metabolic and hemogenic regulation.
Authors
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 SaekiSee AffiliationsHint: Rollover Authors and Affiliations Department of Disease Control, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Department of Radiology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Laboratory of Histology and Cytology, Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
DNAVEC Corporation, Ibaraki 300-2511, Japan
LSI Sapporo Clinic, Sapporo 065-0013, Japan
Department of Reproductive Biology, Center for Regenerative Medicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
The First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan
Department of Nutrition, School of Nursing and Nutrition, Tenshi College, Sapporo 065-0013, Japan
Corresponding authorHighlights
