美国佐治亚大学Stephen Dalton课题组取得最新进展。他们通过近轴中胚层状态进展从人类多能干细胞（hPSC）生成功能性棕色脂肪细胞（BAs）。相关论文于2020年8月11日发表在《细胞-干细胞》杂志上。

在此报告中，hPSC通过近轴中胚层祖细胞状态进行定向分化，该状态可高效生成BA。分子分析确定了BA发展的潜在调控网络，从而深入了解了该谱系的发展。hPSC来源的BA经历了较高效的糖酵解、解偶联的呼吸和脂解速率，这些速率响应于循环AMP（cAMP）依赖性信号传导的变化，与BA组织贮库中的代谢活性一致。移植的人类BAs移植到受体小鼠的肩胛间区域，并表现出产热活性。受体动物的新陈代谢活动、呼吸交换率和全身能量消耗较高。

最后，移植的BAs降低了高血糖动物的循环葡萄糖水平。这些数据为棕色脂肪细胞的产生提供了路线图，并表明从hPSC产生的BA具有作为治疗发展工具的潜力。

据悉，BA是用于治疗包括2型糖尿病在内的代谢疾病的潜在细胞来源。

附：英文原文

Title: Generation of Functional Brown Adipocytes from Human Pluripotent Stem Cells via Progression through a Paraxial Mesoderm State

Author: Liang Zhang, John Avery, Amelia Yin, Amar M. Singh, Timothy S. Cliff, Hang Yin, Stephen Dalton

Issue&Volume: 2020-08-11

Abstract: Brown adipocytes (BAs) are a potential cell source for the treatment of metabolicdisease, including type 2 diabetes. In this report, human pluripotent stem cells (hPSCs)are subject to directed differentiation through a paraxial mesoderm progenitor statethat generates BAs at high efficiency. Molecular analysis identifies potential regulatorynetworks for BA development, giving insight into development along this lineage. hPSC-derivedBAs undergo elevated rates of glycolysis, uncoupled respiration, and lipolysis thatare responsive to changes in cyclic AMP (cAMP)-dependent signaling, consistent withmetabolic activity in BA tissue depots. Transplanted human BAs engraft into the inter-scapularregion of recipient mice and exhibit thermogenic activity. Recipient animals haveelevated metabolic activity, respiratory exchange ratios, and whole-body energy expenditure.Finally, transplanted BAs reduce circulating glucose levels in hyperglycemic animals.These data provide a roadmap for brown adipocyte development and indicate that BAsgenerated from hPSCs have potential as a tool for therapeutic development.

DOI: 10.1016/j.stem.2020.07.013

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30351-9