Utilizing single-cell variations to reveal environment-dependent tuning of network connectivity in human macrophages (single cell RT-PCR)

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. single cells