Abstract：
:Signaling proteins display remarkable cell-to-cell heterogeneity in their dynamic responses to stimuli, but the consequences of this heterogeneity remain largely unknown. For instance, the contribution of the dynamics of the innate immune transcription factor nuclear factor κB (NF-κB) to gene expression output is disputed. Here we explore these questions by integrating live-cell imaging approaches with single-cell sequencing technologies. We used this approach to measure both the dynamics of lipopolysaccharide-induced NF-κB activation and the global transcriptional response in the same individual cell. Our results identify multiple, distinct cytokine expression patterns that are correlated with NF-κB activation dynamics, establishing a functional role for NF-κB dynamics in determining cellular phenotypes. Applications of this approach to other model systems and single-cell sequencing technologies have significant potential for discovery, as it is now possible to trace cellular behavior from the initial stimulus, through the signaling pathways, down to genome-wide changes in gene expression, all inside of a single cell.
journal_name
Cell Systjournal_title
Cell systemsauthors
Lane K,Van Valen D,DeFelice MM,Macklin DN,Kudo T,Jaimovich A,Carr A,Meyer T,Pe'er D,Boutet SC,Covert MWdoi
10.1016/j.cels.2017.03.010subject
Has Abstractpub_date
2017-04-26 00:00:00pages
458-469.e5issue
4eissn
2405-4712issn
2405-4720pii
S2405-4712(17)30132-1journal_volume
4pub_type
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