Single-cell profiling reveals the origin of phenotypic variability in adipogenesis.
Single-cell profiling reveals the origin of phenotypic variability in adipogenesis.
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DOI：
10.1371/journal.pone.0005189
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Cheng JX
中科院分区：
文献类型：
--
作者：
Le TT;Cheng JX
克隆细胞群体中的表型异质性是一种被充分观察但知之甚少的现象。在此，采用单细胞方法来研究3 T3-L1细胞分化为脂肪细胞期间表型异质性的非突变原因。使用相干反斯托克斯拉曼散射显微镜和流式细胞术，脂肪形成基因表达，胰岛素信号传导和葡萄糖输入与单细胞中的脂滴积累同时可视化。成脂基因PPARγ、C/EBPα、aP 2、LP 2的表达表明所有细胞都致力于脂肪细胞分化。然而，在许多分化细胞中缺乏脂滴表明成脂基因表达不足以形成脂滴。相反，脂滴形成中的细胞间变异性取决于胰岛素信号传导途径的级联反应，所述胰岛素信号传导途径包括胰岛素敏感性、激酶活性、葡萄糖输入、胰岛素降解酶的表达和胰岛素降解速率。增加和延长胰岛素刺激促进所有分化细胞中的脂滴积累。单细胞分析揭示了胰岛素信号级联反应的动力学，这是药物诱导脂肪形成中表型变异的起源。
Phenotypic heterogeneity in a clonal cell population is a well-observed but poorly understood phenomenon. Here, a single-cell approach is employed to investigate non-mutative causes of phenotypic heterogeneity during the differentiation of 3T3-L1 cells into fat cells. Using coherent anti-Stokes Raman scattering microscopy and flow cytometry, adipogenic gene expression, insulin signaling, and glucose import are visualized simultaneously with lipid droplet accumulation in single cells. Expression of adipogenic genes PPARγ, C/EBPα, aP2, LP2 suggests a commitment to fat cell differentiation in all cells. However, the lack of lipid droplet in many differentiating cells suggests adipogenic gene expression is insufficient for lipid droplet formation. Instead, cell-to-cell variability in lipid droplet formation is dependent on the cascade responses of an insulin signaling pathway which includes insulin sensitivity, kinase activity, glucose import, expression of an insulin degradation enzyme, and insulin degradation rate. Increased and prolonged insulin stimulation promotes lipid droplet accumulation in all differentiating cells. Single-cell profiling reveals the kinetics of an insulin signaling cascade as the origin of phenotypic variability in drug-inducible adipogenesis.
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影响因子：
48
作者：
Gordon, Andrew;Colman-Lerner, Alejandro;Brent, Roger
通讯作者：
Brent, Roger
影响因子：
20.1
作者：
Fukumura, D;Ushiyama, A;Jain, RK
通讯作者：
Jain, RK
DOI：
10.1126/science.1161427
发表时间：
2008-10-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Choi PJ;Cai L;Frieda K;Xie XS
通讯作者：
Xie XS
DOI：
10.1016/s0167-4889(97)00066-9
发表时间：
1997-09-11
影响因子：
5.1
作者：
Duckworth, WC;Hamel, FG;Peavy, DE
通讯作者：
Peavy, DE
影响因子：
6.5
作者：
Lee, YH;Chen, SY;Huang, YF
通讯作者：
Huang, YF