Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue.
Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue.
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DOI：
10.1016/j.stemcr.2021.01.013
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发表时间：
2021-03-09
影响因子：
5.9
通讯作者：
Vidal-Puig A
中科院分区：
文献类型：
--
作者：
Carobbio S;Guenantin AC;Bahri M;Rodriguez-Fdez S;Honig F;Kamzolas I;Samuelson I;Long K;Awad S;Lukovic D;Erceg S;Bassett A;Mendjan S;Vallier L;Rosen BS;Chiarugi D;Vidal-Puig A
增加棕色脂肪组织（BAT）的质量和活化是治疗肥胖和并发症的治疗策略。肥胖和糖尿病患者的BAT含量较低，因此需要一种有效的方法来扩大其质量。关于人类BAT如何发展、分化和最佳激活的知识有限。考虑到其低容量和解剖学分散性，人类BAT具有挑战性。这些限制使得在人类中进行详细的BAT相关发育和功能机制研究几乎是不可能的。我们已经开发并表征了一种新的化学定义的方案，用于将人多能干细胞（hPSC）分化为棕色脂肪细胞（BA），克服了目前的局限性。该方案一步一步地概括了人类BAT的生理发育路径。获得的BA表达BA和产热标记物，是胰岛素敏感的，并且对β-肾上腺素能刺激有反应。这种新的协议是可扩展的，使人类BA的研究在早期阶段的发展。这是一种将hPSC分化为BA的新颖、稳健和可扩展的方案。该方案概括了人类BAT发育的不同阶段，hPSC衍生的BA显示出真正人类BA的转录组学和功能特征。它代表了用于人类BA分化的时间分析的有用工具。肥胖患者具有少量的BAT，因此需要有效的方法来扩大其质量和活化以治疗肥胖和并发症。关于人类BAT生理学的知识有限，并且访问它具有挑战性。为了克服这一点，Carobbio及其同事开发了一种新的方案，将人类PSC分化为功能性棕色脂肪细胞，重现了人类BAT的发育路径。
Increasing brown adipose tissue (BAT) mass and activation is a therapeutic strategy to treat obesity and complications. Obese and diabetic patients possess low amounts of BAT, so an efficient way to expand their mass is necessary. There is limited knowledge about how human BAT develops, differentiates, and is optimally activated. Accessing human BAT is challenging, given its low volume and anatomical dispersion. These constraints make detailed BAT-related developmental and functional mechanistic studies in humans virtually impossible. We have developed and characterized functionally and molecularly a new chemically defined protocol for the differentiation of human pluripotent stem cells (hPSCs) into brown adipocytes (BAs) that overcomes current limitations. This protocol recapitulates step by step the physiological developmental path of human BAT. The BAs obtained express BA and thermogenic markers, are insulin sensitive, and responsive to β-adrenergic stimuli. This new protocol is scalable, enabling the study of human BAs at early stages of development. This is a novel, robust and scalable protocol to differentiate hPSCs into BAs The protocol recapitulates the different stages of human BAT development hPSC-derived BAs show transcriptomic and functional features of bona fide human BAs It represents a useful tool for temporal analysis of human BAs differentiation Obese patients possess low amounts of BAT, so an efficient way to expand its mass and activation is necessary to treat obesity and complications. There is limited knowledge about human BAT physiology and accessing it is challenging. To overcome this, Carobbio and colleagues developed a new protocol to differentiate human PSCs into functional brown adipocytes, recapitulating human BAT developmental path.
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影响因子：
9.8
作者：
McQuin C;Goodman A;Chernyshev V;Kamentsky L;Cimini BA;Karhohs KW;Doan M;Ding L;Rafelski SM;Thirstrup D;Wiegraebe W;Singh S;Becker T;Caicedo JC;Carpenter AE
通讯作者：
Carpenter AE
影响因子：
3.7
作者：
Markussen LK;Isidor MS;Breining P;Andersen ES;Rasmussen NE;Petersen LI;Pedersen SB;Richelsen B;Hansen JB
通讯作者：
Hansen JB
影响因子：
4.6
作者：
Chal, Jerome;Al Tanoury, Ziad;Pourquie, Olivier
通讯作者：
Pourquie, Olivier
影响因子：
20.8
作者：
de Jong, Jasper M. A.;Sun, Wenfei;Petrovic, Natasa
通讯作者：
Petrovic, Natasa
影响因子：
7.7
作者：
Hanssen, Mark J. W.;van der Lans, Anouk A. J. J.;Lichtenbelt, Wouter D. van Marken
通讯作者：
Lichtenbelt, Wouter D. van Marken