Single-cell RNA-seq reveals dynamic paracrine control of cellular variation.
Single-cell RNA-seq reveals dynamic paracrine control of cellular variation.
复制标题
DOI：
10.1038/nature13437
复制
发表时间：
2014-06-19
期刊：
影响因子：
64.8
通讯作者：
Regev, Aviv
中科院分区：
文献类型：
--
作者：
Shalek, Alex K.;Satija, Rahul;Shuga, Joe;Trombetta, John J.;Gennert, Dave;Lu, Diana;Chen, Peilin;Gertner, Rona S.;Gaublomme, Jellert T.;Yosef, Nir;Schwartz, Schraga;Fowler, Brian;Weaver, Suzanne;Wang, Jing;Wang, Xiaohui;Ding, Ruihua;Raychowdhury, Raktima;Friedman, Nir;Hacohen, Nir;Park, Hongkun;May, Andrew P.;Regev, Aviv
高通量单细胞转录组学提供了一种无偏的方法，可以理解看似相同的细胞之间基因表达变化的程度，基础和功能。细胞（DC）跨越了几个实验条件。在表达细胞内表达给定的mRNA和转录水平。在所有细胞中。表明这种反应是通过干扰素介导的旁分泌信号进行协调的。我们的研究。建立复杂的动态响应。
High-throughput single-cell transcriptomics offers an unbiased approach for understanding the extent, basis, and function of gene expression variation between seemingly identical cells. Here, we sequence single-cell RNA-Seq libraries prepared from over 1,700 primary mouse bone marrow derived dendritic cells (DCs) spanning several experimental conditions. We find substantial variation between identically stimulated DCs, in both the fraction of cells detectably expressing a given mRNA and the transcript’s level within expressing cells. Distinct gene modules are characterized by different temporal heterogeneity profiles. In particular, a “core” module of antiviral genes is expressed very early by a few “precocious” cells, but is later activated in all cells. By stimulating cells individually in sealed microfluidic chambers, analyzing DCs from knockout mice, and modulating secretion and extracellular signaling, we show that this response is coordinated via interferon-mediated paracrine signaling. Surprisingly, preventing cell-to-cell communication also substantially reduces variability in the expression of an early-induced “peaked” inflammatory module, suggesting that paracrine signaling additionally represses part of the inflammatory program. Our study highlights the importance of cell-to-cell communication in controlling cellular heterogeneity and reveals general strategies that multicellular populations use to establish complex dynamic responses.
登录
查看更多内容
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
9.9
作者：
Rand, Ulfert;Rinas, Melanie;Schwerk, Johannes;Noehren, Gesa;Linnes, Melanie;Kroeger, Andrea;Flossdorf, Michael;Kaly-Kullai, Kristof;Hauser, Hansjoerg;Hoefer, Thomas;Koester, Mario
通讯作者：
Koester, Mario
DOI：
10.1126/science.1179050
发表时间：
2009-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amit I;Garber M;Chevrier N;Leite AP;Donner Y;Eisenhaure T;Guttman M;Grenier JK;Li W;Zuk O;Schubert LA;Birditt B;Shay T;Goren A;Zhang X;Smith Z;Deering R;McDonald RC;Cabili M;Bernstein BE;Rinn JL;Meissner A;Root DE;Hacohen N;Regev A
通讯作者：
Regev A
影响因子：
7.3
作者：
Lee, Timothy K.;Denny, Elissa M.;Covert, Markus W.
通讯作者：
Covert, Markus W.
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP