生物谷 訊 斯坦福大學(xué)的研究人員使用一種新技術(shù)觀察單一細(xì)胞在細(xì)胞信號(hào)復(fù)雜系統(tǒng)中的應(yīng)答反應(yīng),，首次發(fā)現(xiàn)相同細(xì)胞之間存在大范圍的差異,。他們的這項(xiàng)研究結(jié)果發(fā)布在6月27日Nature的在線版本上,。這項(xiàng)研究的負(fù)責(zé)人是生物工程學(xué)助理教授Markus Covert。
到目前為止,，大部分關(guān)于細(xì)胞信號(hào)的信息是通過(guò)整體分析方法觀察細(xì)胞群獲得的,。由于技術(shù)上的限制科學(xué)家不能觀察單獨(dú)的細(xì)胞,。該研究使用了一種基于微流體的成像系統(tǒng)，結(jié)果表明科學(xué)家的一些認(rèn)識(shí)可能已經(jīng)被基于細(xì)胞群體研究的結(jié)果所誤導(dǎo),。
研究人員表示,，細(xì)胞活化這一結(jié)果是一樣的，然而細(xì)胞達(dá)到結(jié)果的過(guò)程可能是不一樣的,，群體研究不能顯示信息錯(cuò)綜復(fù)雜的信號(hào)網(wǎng)絡(luò)中的差異,，而這在單一細(xì)胞水平中可以觀察到。
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細(xì)胞信號(hào)交流調(diào)控著基本的細(xì)胞活性以及人體中相應(yīng)的細(xì)胞活動(dòng),。細(xì)胞準(zhǔn)確應(yīng)答周?chē)h(huán)境的能力是發(fā)育，組織修復(fù)和免疫的基礎(chǔ),。深入理解細(xì)胞間的相互交流將有助于了解生物系統(tǒng)的復(fù)雜性,，或能開(kāi)發(fā)出癌癥，糖尿病及其他自身免疫疾病的新療法,。
為了研究單獨(dú)細(xì)胞在細(xì)胞信號(hào)傳導(dǎo)過(guò)程中的反應(yīng),，Covert和Stephen Quake教授的實(shí)驗(yàn)室進(jìn)行了聯(lián)合研究。三年前,，曾有研究人員在Quake的實(shí)驗(yàn)室中開(kāi)發(fā)出了一種微流體芯片技術(shù)針對(duì)性地用于單一細(xì)胞的研究,。在這項(xiàng)研究中，他們就是使用微流體芯片技術(shù)觀察炎癥細(xì)胞的反應(yīng),，也是該技術(shù)在生物學(xué)上的一個(gè)巧妙應(yīng)用,。
在這項(xiàng)研究中，研究人員用不同的蛋白濃縮物刺激細(xì)胞,，這些濃縮物是免疫系統(tǒng)應(yīng)答炎癥或癌癥反應(yīng)的代表性物質(zhì),。結(jié)果發(fā)現(xiàn)，一些細(xì)胞接受信號(hào)并被激活,，而一些細(xì)胞則沒(méi)有激活,。在圖像中，科研人員觀察到細(xì)胞以不同的方式產(chǎn)生應(yīng)答,，但是細(xì)胞的基本反應(yīng)在許多方面是一致的,。（生物谷www.bioon.net）
了解更多
Science Signaling：細(xì)胞信號(hào)傳導(dǎo)通路最優(yōu)新模型
Nature子刊：超魅力小珠調(diào)控細(xì)胞信號(hào)
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生物谷推薦原文出處：
Nature doi:10.1038/nature09145
Single-cell NF-κB dynamics reveal digital activation and analogue information processing
Sava? Tay1,2,4, Jacob J. Hughey1,4, Timothy K. Lee1, Tomasz Lipniacki3, Stephen R. Quake1,2 & Markus W. Covert1
Department of Bioengineering, Stanford University, Stanford, California 94305, USA
Howard Hughes Medical Institute, Stanford, California 94305, USA
Institute of Fundamental Technological Research, Warsaw 02-106, Poland
Cells operate in dynamic environments using extraordinary communication capabilities that emerge from the interactions of genetic circuitry. The mammalian immune response is a striking example of the coordination of different cell types1. Cell-to-cell communication is primarily mediated by signalling molecules that form spatiotemporal concentration gradients, requiring cells to respond to a wide range of signal intensities2. Here we use high-throughput microfluidic cell culture3 and fluorescence microscopy, quantitative gene expression analysis and mathematical modelling to investigate how single mammalian cells respond to different concentrations of the signalling molecule tumour-necrosis factor (TNF)-α, and relay information to the gene expression programs by means of the transcription factor nuclear factor (NF)-κB. We measured NF-κB activity in thousands of live cells under TNF-α doses covering four orders of magnitude. We find, in contrast to population-level studies with bulk assays2, that the activation is heterogeneous and is a digital process at the single-cell level with fewer cells responding at lower doses. Cells also encode a subtle set of analogue parameters to modulate the outcome; these parameters include NF-κB peak intensity, response time and number of oscillations. We developed a stochastic mathematical model that reproduces both the digital and analogue dynamics as well as most gene expression profiles at all measured conditions, constituting a broadly applicable model for TNF-α-induced NF-κB signalling in various types of cells. These results highlight the value of high-throughput quantitative measurements with single-cell resolution in understanding how biological systems operate.
