Single-cell RNA-seq reveals dynamic paracrine control of cellular variation
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Regev_Single cell.pdf
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Author(s)
Satija, Rahul
Shuga, Joe
Trombetta, John J.
Gennert, David
Chen, Peilin
Gertner, Rona S.
Gaublomme, Jellert T.
Yosef, Nir
Schwartz, Schraga
Fowler, Brian
Date Issued
June 2014
Journal
Nature
Publisher
Nature Publishing Group
Citation
Shalek, Alex K., Rahul Satija, Joe Shuga, John J. Trombetta, Dave Gennert, Diana Lu, Peilin Chen, et al. “Single-Cell RNA-Seq Reveals Dynamic Paracrine Control of Cellular Variation.” Nature (June 11, 2014).
Version
Author's final manuscript
Abstract
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 spanning several experimental conditions. We find substantial variation between identically stimulated dendritic cells, in both the fraction of cells detectably expressing a given messenger RNA 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 in response to uniform stimulation with a pathogenic component, but is later activated in all cells. By stimulating cells individually in sealed microfluidic chambers, analysing dendritic cells from knockout mice, and modulating secretion and extracellular signalling, we show that this response is coordinated by interferon-mediated paracrine signalling from these precocious cells. Notably, preventing cell-to-cell communication also substantially reduces variability between cells in the expression of an early-induced ‘peaked’ inflammatory module, suggesting that paracrine signalling 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 can use to establish complex dynamic responses.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1038/nature13437
