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Gottschalk, R. A., & Germain, R. N. (2024). Linking signal input, cell state, and spatial context to inflammatory responses. Current Opinion in Immunology, 91, 102462. Added by: Dr. Enrique Feoli (08/07/2025, 16:02) Last edited by: Dr. Enrique Feoli (08/07/2025, 16:09) |
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| Resource type: Journal Article DOI: 10.1016/j.coi.2024.102462 ID no. (ISBN etc.): 0952-7915 BibTeX citation key: Gottschalk2024 View all bibliographic details  |
Categories: BioAcyl Corp, BioAcyl Corp Subcategories: Microecoambiente, Microenvironment Creators: Germain, Gottschalk Collection: Current Opinion in Immunology |
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| Abstract |
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Signal integration is central to a causal understanding of appropriately scaled inflammatory responses. Here we discuss recent progress in our understanding of the stimulus-response linkages downstream of pro-inflammatory inputs, with special attention to (i) the impact of cell state on the specificity of evoked gene expression and (ii) the critical role of the spatial context of stimulus exposure. Advances in these directions are emerging from new tools for inferring cell-cell interactions and the activities of cytokines and TFs in complex microenvironments, enabling analysis of signal integration in tissue settings. Building on data-driven elucidation of factors driving inflammatory outcomes, mechanistic modeling can then contribute to a quantitative understanding of regulatory events that balance protective versus pathological inflammation.
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| Notes |
 (A) Gene-specific mechanisms support decoding of TF activity. Binding of TFs to regulatory elements (depicted as rectangles) is tuned by both chromatin accessibility and the binding of competitive or cooperative factors. These is evidence for high selectivity of these mechanisms across promoters and enhancers. (B) Cell-state dependent proteomic and epigenetic variation shape stimulus-gene relationships. In the example shown, cell state-dependent changes in chromatin accessibility, competitor protein abundance, and receptor expression would result in varied gene expression patters even with equivalent levels of NFkB activity; some genes with increased chromatin accessibility would be elevated, whereas other genes would show decreased expression due to higher expression of competitor proteins or lower capacity for cytokine signaling.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |