Production of Functional Classical Brown Adipocytes from Human Pluripotent Stem Cells using Specific Hemopoietin Cocktail without Gene Transfer
Production of Functional Classical Brown Adipocytes from Human Pluripotent Stem Cells using Specific Hemopoietin Cocktail without Gene Transfer
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DOI：
10.1016/j.cmet.2012.08.001
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发表时间：
2012-09-05
期刊：
影响因子：
29
通讯作者：
Saeki, Kumiko
中科院分区：
文献类型：
--
作者：
Nishio, Miwako;Yoneshiro, Takeshi;Saeki, Kumiko
棕色脂肪组织因其抗肥胖作用而备受关注；然而，它的发展和参与代谢改善仍然难以捉摸。在这里，我们建立了一种方法，利用特定的造血素鸡尾酒(HC)，在没有外源基因转移的情况下，将人多能干细胞(HPSCs)高效(>；90%)分化为有功能的经典棕色脂肪细胞(BAs)。没有HC和缺乏HC诱导的白色脂肪细胞(WA)标记物的表达，就不会产生BA。HPSC来源的BA(HPSCdBA)可通过刺激β-肾上腺素能受体(AdrRβ)激活呼吸和生热，并增强脂质和糖耐量，而人多能基质细胞来源的WA(HMSCdWA)改善血脂但抑制糖代谢。HPSCdBA共移植可使hMSCdWA诱导的糖耐量降低。令人惊讶的是，hPSCdBA表达各种造血素基因，作为髓系祖细胞的基质。此外，AdrRβ刺激可促进化疗引起的骨髓抑制的恢复。我们的研究加深了我们对BA的理解，确定了BA在代谢和血液调节中的作用。
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 beta-adrenergic receptor (AdrR beta) 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, AdrR beta stimuli enhanced recovery from chemotherapy-induced myelosuppression. Our study enhances our understanding of BA, identifying roles in metabolic and hemogenic regulation.