Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat
Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat
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DOI：
10.1073/pnas.1010929108
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发表时间：
2011-01-04
影响因子：
11.1
通讯作者：
Tseng, Yu-Hua
中科院分区：
文献类型：
--
作者：
Schulz, Tim J.;Huang, Tian Lian;Tseng, Yu-Hua
棕色脂肪专门用于能量消耗，因此已被提议用作抵抗肥胖的防御。尽管最近的进展描绘棕色脂肪细胞分化的转录调控，细胞谱系规范和发展线索指定棕色脂肪细胞的命运仍然知之甚少。在这项研究中，我们鉴定并分离了存在于小鼠棕色脂肪、白色脂肪和骨骼肌中的成脂祖细胞（Sca-1（+）/CD 45（-）/Mac 1（-）;称为Sca-1（+）祖细胞，ScaPCs）亚群。来自不同组织的ScaPC具有独特的分子表达特征和成脂能力。重要的是，尽管来自肩胛间棕色脂肪组织（BAT）的ScaPC是组成型定向的棕色脂肪祖细胞，但来自骨骼肌和皮下白色脂肪的Sca-1+细胞在用骨形态发生蛋白7（BMP 7）刺激后高度可诱导分化成棕色样脂肪细胞。与这些发现一致，与从肠系膜或网膜白色脂肪分离的细胞相比，从皮下白色脂肪分离的人前脂肪细胞也表现出最大的诱导能力，成为棕色脂肪细胞。当肌肉驻留的ScaPC被重新移植到同基因小鼠的骨骼肌中时，BMP 7处理的ScaPC有效地发育成具有棕色脂肪特异性特征的脂肪组织。重要的是，与从肥胖倾向小鼠分离的细胞相比，来自肥胖抵抗小鼠的ScaPC表现出明显更高的产热能力。这些数据建立了组织驻留脂肪祖细胞的分子特征，并证明了这些祖细胞和诱导信号之间的动态相互作用，共同作用，以指定棕色脂肪细胞的发展。
Brown fat is specialized for energy expenditure and has therefore been proposed to function as a defense against obesity. Despite recent advances in delineating the transcriptional regulation of brown adipocyte differentiation, cellular lineage specification and developmental cues specifying brown-fat cell fate remain poorly understood. In this study, we identify and isolate a subpopulation of adipogenic progenitors (Sca-1(+)/CD45(-)/Mac1(-); referred to as Sca-1(+) progenitor cells, ScaPCs) residing in murine brown fat, white fat, and skeletal muscle. ScaPCs derived from different tissues possess unique molecular expression signatures and adipogenic capacities. Importantly, although the ScaPCs from interscapular brown adipose tissue (BAT) are constitutively committed brown-fat progenitors, Sca-1+ cells from skeletal muscle and subcutaneous white fat are highly inducible to differentiate into brown-like adipocytes upon stimulation with bone morphogenetic protein 7 (BMP7). Consistent with these findings, human preadipocytes isolated from subcutaneous white fat also exhibit the greatest inducible capacity to become brown adipocytes compared with cells isolated from mesenteric or omental white fat. When muscle-resident ScaPCs are re-engrafted into skeletal muscle of syngeneic mice, BMP7-treated ScaPCs efficiently develop into adipose tissue with brown fat-specific characteristics. Importantly, ScaPCs from obesity-resistant mice exhibit markedly higher thermogenic capacity compared with cells isolated from obesity-prone mice. These data establish the molecular characteristics of tissue-resident adipose progenitors and demonstrate a dynamic interplay between these progenitors and inductive signals that act in concert to specify brown adipocyte development.