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Signals trigger state-specific transcriptional programs to support diversity and homeostasis in immune cells

Item Type:Article
Title:Signals trigger state-specific transcriptional programs to support diversity and homeostasis in immune cells
Creators Name:Fischer, C. and Metsger, M. and Bauch, S. and Vidal, R. and Böttcher, M. and Grote, P. and Kliem, M. and Sauer, S.
Abstract:Macrophages play key roles in the immune systems of humans and other mammals. Here, we performed single-cell analyses of the mRNAs and proteins of human macrophages to compare their responses to the signaling molecules lipopolysaccharide (LPS), a component of Gram-negative bacteria, and palmitate (PAL), a free fatty acid. We found that, although both molecules signal through the cell surface protein Toll-like receptor 4 (TLR4), they stimulated the expression of different genes, resulting in specific pro- and anti-inflammatory cellular states for each signal. The effects of the glucocorticoid receptor, which antagonizes LPS signaling, and cyclic AMP-dependent transcription factor 3, which inhibits PAL-induced inflammation, on inflammatory response seemed largely determined by digital on-off events. Furthermore, the quantification of transcriptional variance and signaling entropy enabled the identification of cell state-specific deregulated molecular pathways. These data suggest that the preservation of signaling in distinct cells might confer diversity on macrophage populations essential to maintaining major cellular functions.
Keywords:Activating Transcription Factor 3, Gene Expression Regulation, Genetic Transcription, Genetic Variation, Homeostasis, Interleukin-1beta, Interleukin-8, Lipopolysaccharides, Macrophages, Palmitates, Signal Transduction, Single-Cell Analysis, THP-1 Cells, Toll-Like Receptor 4
Source:Science Signaling
Publisher:American Association for the Advancement of Science
Page Range:eaao5820
Date:14 May 2019
Official Publication:https://doi.org/10.1126/scisignal.aao5820
PubMed:View item in PubMed

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