Utilizing single-cell variations to reveal environment-dependent tuning of network connectivity in human macrophages (RNA-Seq, CAGE and ChIP-Seq)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE80727 | GEO | 2017/03/27
REPOSITORIES: GEO
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Project description:Cell-to-cell expression variation is a prevalent feature of cell populations, but the environmental, cellular and biochemical conditions under which variability in the level of one gene can or cannot be propagated to affect that of other genes in the underlying network within cells remain poorly understood. Here we explore this issue using single-cell qPCR and bulk-level RNAseq, CAGE, and ChIPseq analysis of human macrophages exposed to different cytokine environments. Our analyses reveal that cellular adaptation to different environments could involve tuning the extent of such variability (or information) propagation (IP) in the network, thereby shaping environment-dependent patterns of gene-gene correlations and phenotypic heterogeneity across single cells. We find that IP can be regulated through modification of multiple network and signaling parameters, such as the degree of transcription factor-chromatin interactions. Our findings thus suggest that adaptive IP may be a widespread, yet underexplored, aspect of cellular adaptation to distinct environments.
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Project description:Utilizing single-cell variations to reveal environment-dependent tuning of network connectivity in human macrophages
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Project description:Oral streptococci metabolize carbohydrate to produce organic acids, which not only decrease the environmental pH, but also increase osmolality of dental plaque fluid due to tooth demineralization and consequent calcium and phosphate accumulation. Despite these unfavorable environmental changes, the bacteria continue to thrive. The aim of this study was to obtain a global view on strategies taken by Streptococcus mutans to deal with physiologically relevant elevated osmolality, and perseveres within a cariogenic dental plaque. We investigated phenotypic change of S. mutans biofilm upon hyperosmotic challenge. We found that the hyperosmotic condition was able to initiate S. mutans biofilm dispersal by reducing both microbial content and extracellular polysaccharides matrix. We then used whole-genome microarray with quantitative RT-PCR validation to systemically investigate the underlying molecular machineries of this bacterium in response to the hyperosmotic stimuli. Among those identified 40 deferentially regulated genes, down-regulation of gtfB and comC were believed to be responsible for the observed biofilm dispersal. Further analysis of microarray data showed significant up-regulation of genes and pathways involved in carbohydrate metabolism. Specific genes involved in heat shock response and acid tolerance were also upregulated, indicating potential cross-talk between hyperosmotic and other environmental stress. Hyperosmotic condition induces significant stress response on S. mutans at both phenotypic and transcriptomic levels. In the meantime, it may take full advantage of these environmental stimuli to better fit the fluctuating environments within oral cavity, and thus emerges as numeric-predominant bacterium under cariogenic conditions.
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