Environment Tunes Propagation of Cell-to-Cell Variation in the Human Macrophage Gene Network.

Autor:	Martins AJ; Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institutes of Health, Bethesda, MD 20892, USA., Narayanan M; Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institutes of Health, Bethesda, MD 20892, USA., Prüstel T; Computational Biology Section, Laboratory of Systems Biology, National Institutes of Health, Bethesda, MD 20892, USA., Fixsen B; Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institutes of Health, Bethesda, MD 20892, USA., Park K; Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institutes of Health, Bethesda, MD 20892, USA; Biophysics Program, University of Maryland-NIH Graduate Partnership Program, University of Maryland, College Park, MD 20742, USA., Gottschalk RA; Lymphocyte Biology Section, Laboratory of Systems Biology, National Institutes of Health, Bethesda, MD 20892, USA., Lu Y; Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institutes of Health, Bethesda, MD 20892, USA., Andrews-Pfannkoch C; Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institutes of Health, Bethesda, MD 20892, USA., Lau WW; Office of Intramural Research, Center for Information Technology, National Institutes of Health, Bethesda, MD 20892, USA., Wendelsdorf KV; Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institutes of Health, Bethesda, MD 20892, USA., Tsang JS; Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institutes of Health, Bethesda, MD 20892, USA; Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: john.tsang@nih.gov.
Jazyk:	angličtina
Zdroj:	Cell systems [Cell Syst] 2017 Apr 26; Vol. 4 (4), pp. 379-392.e12. Date of Electronic Publication: 2017 Mar 29.
DOI:	10.1016/j.cels.2017.03.002
Abstrakt:	Cell-to-cell variation in gene expression and the propagation of such variation (PoV or "noise propagation") from one gene to another in the gene network, as reflected by gene-gene correlation across single cells, are commonly observed in single-cell transcriptomic studies and can shape the phenotypic diversity of cell populations. While gene network "rewiring" is known to accompany cellular adaptation to different environments, how PoV changes between environments and its underlying regulatory mechanisms are less understood. Here, we systematically explored context-dependent PoV among genes in human macrophages, utilizing different cytokines as natural perturbations of multiple molecular parameters that may influence PoV. Our single-cell, epigenomic, computational, and stochastic simulation analyses reveal that environmental adaptation can tune PoV to potentially shape cellular heterogeneity by changing parameters such as the degree of phosphorylation and transcription factor-chromatin interactions. This quantitative tuning of PoV may be a widespread, yet underexplored, property of cellular adaptation to distinct environments. (Copyright © 2017. Published by Elsevier Inc.)
Databáze:	MEDLINE
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