Genetic and functional characterization of clonally derived adult human brown adipocytes.
Genetic and functional characterization of clonally derived adult human brown adipocytes.
复制标题
克隆衍生的成年人类棕色脂肪细胞的遗传和功能表征。
DOI：
10.1038/nm.3819
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发表时间：
2015-04
期刊：
影响因子：
82.9
通讯作者：
Kajimura, Shingo
中科院分区：
文献类型：
--
作者：
Shinoda, Kosaku;Luijten, Ineke H. N.;Hasegawa, Yutaka;Hong, Haemin;Sonne, Si B.;Kim, Miae;Xue, Ruidan;Chondronikola, Maria;Cypess, Aaron M.;Tseng, Yu-Hua;Nedergaard, Jan;Sidossis, Labros S.;Kajimura, Shingo
棕色脂肪组织（BAT）在哺乳动物中作为对抗体温过低的天然防御系统，并且其激活至增加的能量消耗状态被认为可以防止肥胖的发展。尽管BAT在成年人中的存在已被广泛认可，但其细胞来源和分子身份仍然难以捉摸，主要是因为各种脂肪组织库内的高度细胞异质性。为了了解单个细胞分辨率下成人棕色脂肪细胞的性质，我们从来自两个个体的成人BAT的基质血管组分中分离克隆衍生的脂肪细胞，并全面分析其分子特征。我们使用RNA测序，然后进行无偏的全基因组表达分析，发现解偶联蛋白1（UCP1）阳性的人脂肪细胞群体具有类似于可招募的产热脂肪细胞（即米色脂肪细胞）的分子特征。此外，我们还鉴定了在UCP1阳性人脂肪细胞中高度富集的分子标记物，包括钾通道K3（KCNK3）和线粒体肿瘤抑制因子1（MTUS1）。此外，我们使用功能丧失的方法对这两种标记进行功能表征，发现KCNK3和MTUS1是米色脂肪细胞分化和产热功能所需的。这项研究的结果为人类BAT研究提供了新的机会，例如促进基于细胞的疾病建模和产热调节剂的无偏筛选。
Brown adipose tissue (BAT) acts in mammals as a natural defense system against hypothermia, and its activation to a state of increased energy expenditure is believed to protect against the development of obesity. Even though the existence of BAT in adult humans has been widely appreciated, its cellular origin and molecular identity remain elusive largely because of high cellular heterogeneity within various adipose tissue depots. To understand the nature of adult human brown adipocytes at single cell resolution, we isolated clonally derived adipocytes from stromal vascular fractions of adult human BAT from two individuals and globally analyzed their molecular signatures. We used RNA sequencing followed by unbiased genome-wide expression analyses and found that a population of uncoupling protein 1 (UCP1)-positive human adipocytes possessed molecular signatures resembling those of a recruitable form of thermogenic adipocytes (that is, beige adipocytes). In addition, we identified molecular markers that were highly enriched in UCP1-positive human adipocytes, a set that included potassium channel K3 (KCNK3) and mitochondrial tumor suppressor 1 (MTUS1). Further, we functionally characterized these two markers using a loss-of-function approach and found that KCNK3 and MTUS1 were required for beige adipocyte differentiation and thermogenic function. The results of this study present new opportunities for human BAT research, such as facilitating cell-based disease modeling and unbiased screens for thermogenic regulators.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
7.7
作者：
Saito M;Okamatsu-Ogura Y;Matsushita M;Watanabe K;Yoneshiro T;Nio-Kobayashi J;Iwanaga T;Miyagawa M;Kameya T;Nakada K;Kawai Y;Tsujisaki M
通讯作者：
Tsujisaki M
影响因子：
18.2
作者：
Kajimura S;Saito M
通讯作者：
Saito M
影响因子：
2.7
作者：
Atit, Radhika;Sgaier, Sema K.;Conlon, Ronald A.
通讯作者：
Conlon, Ronald A.
影响因子：
4.7
作者：
Inoue, Masurni;Harada, Keita;Warashina, Akira
通讯作者：
Warashina, Akira