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首页> 外文期刊>Cell metabolism >Production of functional classical brown adipocytes from human pluripotent stem cells using specific hemopoietin cocktail without gene transfer
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Production of functional classical brown adipocytes from human pluripotent stem cells using specific hemopoietin cocktail without gene transfer

机译：使用特定的造血素混合物从人类多能干细胞生产功能性经典棕色脂肪细胞而无需基因转移

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摘要

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.
机译：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，我们建立了一种使用特定的造血素混合物（HC）无需外源基因转移即可将人类多能干细胞（hPSCs）高效分化为功能性经典棕色脂肪细胞（BAs）的方法。没有HC不会生成BA，并且缺少HC诱导的白色脂肪细胞（WA）标记表达的成分。 hPSC衍生的BA（hPSCdBA）通过β-肾上腺素能受体（AdrRβ）刺激显示呼吸和热激活，并增强了脂质和葡萄糖耐受性，而人多能基质细胞衍生的WA（hMSCdWA）改善了脂质，但抑制了葡萄糖代谢。 hPSCdBA的共移植可标准化hMSCdWA诱导的葡萄糖耐量异常。令人惊讶的是，hPSCdBAs表达了多种造血素基因，作为骨髓祖细胞的基质。此外，AdrRβ刺激增强了化疗诱导的骨髓抑制的恢复。我们的研究增强了我们对BA的了解，确定了其在代谢和血液调节中的作用。

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