Heterogeneity in the physiological states and pharmacological responses of differentiating 3T3-L1 preadipocytes.
Heterogeneity in the physiological states and pharmacological responses of differentiating 3T3-L1 preadipocytes.
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DOI：
10.1083/jcb.200904140
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发表时间：
2009-11-02
期刊：
影响因子：
--
通讯作者：
Wu LF
中科院分区：
文献类型：
--
作者：
Loo LH;Lin HJ;Singh DK;Lyons KM;Altschuler SJ;Wu LF
基于系统生物学的分析表明，分化的脂肪细胞在单细胞水平上看起来非常不同，并形成不同的细胞亚群。脂肪生成和脂肪分解途径关键成分的增加在脂肪生成过程中与人群平均水平相关。然而，分化的前脂肪细胞在细胞和脂滴（LD）形态方面具有高度异质性，并且单个细胞遵循群体平均趋势的程度尚不清楚。在这项研究中，我们使用免疫荧光显微镜分析了分化 3T3-L1 前脂肪细胞的分子异质性。出乎意料的是，我们只观察到一小部分细胞同时高表达脂肪生成标记物（过氧化物酶体增殖物激活受体 γ [PPARγ]、CCAAT/增强子结合蛋白 α 和脂联素）和脂质积累标记物（激素敏感脂肪酶、周脂肪素 A 和 LD）。相反，我们识别出与这些读数的表达负相关的细胞亚群。 PPARγ 激动剂、毛喉素和脂肪酸对脂肪细胞分化的急性扰动诱导了亚群特异性效应，包括观察到的亚群中细胞百分比的重新分布和 PPARγ 的差异表达水平。总的来说，我们的结果表明，3T3-L1 脂肪生成过程中观察到的异质性反映了具有不同生理状态的亚群的动态混合。
A systems biology–based analysis shows that differentiating adipocytes look very different at the single-cell level and form distinct cellular subpopulations. Increases in key components of adipogenesis and lipolysis pathways correlate at the population-averaged level during adipogenesis. However, differentiating preadipocytes are highly heterogeneous in cellular and lipid droplet (LD) morphologies, and the degree to which individual cells follow population-averaged trends is unclear. In this study, we analyze the molecular heterogeneity of differentiating 3T3-L1 preadipocytes using immunofluorescence microscopy. Unexpectedly, we only observe a small percentage of cells with high simultaneous expression of markers for adipogenesis (peroxisome proliferator-activated receptor γ [PPARγ], CCAAT/enhancer-binding protein α, and adiponectin) and lipid accumulation (hormone-sensitive lipase, perilipin A, and LDs). Instead, we identify subpopulations of cells with negatively correlated expressions of these readouts. Acute perturbation of adipocyte differentiation with PPARγ agonists, forskolin, and fatty acids induced subpopulation-specific effects, including redistribution of the percentage of cells in observed subpopulations and differential expression levels of PPARγ. Collectively, our results suggested that heterogeneity observed during 3T3-L1 adipogenesis reflects a dynamic mixture of subpopulations with distinct physiological states.
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影响因子：
3.7
作者：
Le TT;Cheng JX
通讯作者：
Cheng JX
DOI：
10.1002/cyto.990060610
发表时间：
1985-01-01
期刊：
CYTOMETRY
影响因子：
--
作者：
GRATZNER, HG;AHMAD, PM;AHMAD, F
通讯作者：
AHMAD, F
影响因子：
48
作者：
Loo, Lit-Hsin;Wu, Lani F.;Altschuler, Steven J.
通讯作者：
Altschuler, Steven J.
影响因子：
7.7
作者：
Iwaki, M;Matsuda, M;Shimomura, I
通讯作者：
Shimomura, I
影响因子：
4.8
作者：
Hannah, VC;Ou, JF;Brown, MS
通讯作者：
Brown, MS