title: Production of functional classical brown adipocytes from human pluripotent stem cells using specific hemopoietin cocktail without gene transfer.
abstract: 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.
authors.affiliation: Department of Disease Control, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Nishio
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoneshiro
authors.forename: Masako
authors.initials: M
authors.lastname: Nakahara
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Suzuki
authors.forename: Koichi
authors.initials: K
authors.lastname: Saeki
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawai
authors.forename: Hidenori
authors.initials: H
authors.lastname: Akutsu
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yasuda
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Akira
authors.initials: A
authors.lastname: Yuo
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kubota
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saito
authors.forename: Kumiko
authors.initials: K
authors.lastname: Saeki
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D005951:Glucose Tolerance Test; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008854:Microscopy, Electron; D039904:Pluripotent Stem Cells / Q000166:cytology*; D060888:Real-Time Polymerase Chain Reaction; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022722:Thermogenesis / Q000502:physiology
chemical_list: D016298:Hematopoietic Cell Growth Factors; D011943:Receptors, Adrenergic, beta