Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-B activation
Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-B activation
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激酶信号复合物内的正反馈作为 NF-的开关机制
DOI：
10.1016/j.bpj.2014.10.002
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发表时间：
2014
期刊：
影响因子：
56.9
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Shinohara;H.;Behar;M.;Inoue;K.;Hiroshima;M.;Yasusda;T.;Nagashima;T.;Kimura;S.;Sanjo;H.;Maeda;S.;Yumoto;N.;Ki;S.;Akira;S.;Sako;Y.;Hoffman;A.;Kurosaki;T.;and Okada-Hatakeyama;M.
细胞分化沿着复杂的途径进行，即使是由细胞外信号分子诱导的。这种复杂性的主要原因之一是细胞的高度多维内部动力学，有时会导致单个细胞对细胞外刺激产生明显的随机反应。因此，为了了解细胞分化，有必要以单细胞分辨率监测细胞的内部动态。在这里，我们使用单细胞的拉曼和自发荧光光谱分析来检测细胞内分子成分的动态变化。 MCF-7 细胞是一种人类癌症来源的细胞系，通过在培养基中添加调蛋白 (HRG) 可以诱导其分化为乳腺样细胞。我们测量了 12 天 HRG 刺激期间 MCF-7 细胞细胞质中的光谱。拉曼散射光谱是信号的主要组成部分，随着时间的推移而变化。拉曼光谱的多组分分析表明，细胞内分子主要成分（包括蛋白质和脂质）的动力学沿着分化途径周期性变化。拉曼散射的背景自发荧光信号也提供了有关分化过程的信息。利用拉曼光谱和自发荧光光谱的全部信息，我们能够可视化多组分相空间中细胞分化的途径。
Cellular differentiation proceeds along complicated pathways, even when it is induced by extracellular signaling molecules. One of the major reasons for this complexity is the highly multidimensional internal dynamics of cells, which sometimes causes apparently stochastic responses in individual cells to extracellular stimuli. Therefore, to understand cell differentiation, it is necessary to monitor the internal dynamics of cells at single-cell resolution. Here, we used a Raman and autofluorescence spectrum analysis of single cells to detect dynamic changes in intracellular molecular components. MCF-7 cells are a human cancer-derived cell line that can be induced to differentiate into mammary-gland-like cells with the addition of heregulin (HRG) to the culture medium. We measured the spectra in the cytoplasm of MCF-7 cells during 12 days of HRG stimulation. The Raman scattering spectrum, which was the major component of the signal, changed with time. A multicomponent analysis of the Raman spectrum revealed that the dynamics of the major components of the intracellular molecules, including proteins and lipids, changed cyclically along the differentiation pathway. The background autofluorescence signals of Raman scattering also provided information about the differentiation process. Using the total information from the Raman and autofluorescence spectra, we were able to visualize the pathway of cell differentiation in the multicomponent phase space.