Environment drives selection and function of enhancers controlling tissue-specific macrophage identities
By D. Gosselin, Verena M. Link, C. Romanoski, G. Fonseca, Dawn Z. Eichenfield, Nathan Spann, Joshua D Stender, H. Chun, Hannah Garner, F. Geissmann and 1 more. Cell, 2014
736 citations recorded by the source corpus.
SUMMARY Macrophages reside in essentially all tissues of the body and play key roles in innate and adaptive immune responses. Distinct populations of tissue macrophages also acquire context-specific functions that are important for normal tissue homeostasis. To investigate mechanisms responsible for tissue-specific functions, we analyzed the transcriptomes and enhancer landscapes of brain microglia and resident macrophages of the peritoneal cavity. In addition, we exploited natural genetic variation as a genome-wide ‘mutagenesis’ strategy to identify DNA recognition motifs for transcription factors that promote common or subset-specific binding of the macrophage lineage-determining factor PU.1. We find that distinct tissue environments drive divergent programs of gene expression by differentially activating a common enhancer repertoire and by inducing the expression of divergent secondary transcription factors that collaborate with PU.1 to establish tissue–specific enhancers. These findings provide insights into molecular mechanisms by which tissue environment influences macrophage phenotypes that are likely to be broadly applicable to other cell types.
Subfields: Biological Psychiatry, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/2bd4a9c9166a9f136a512edf5eb732e4ea6e66b8
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In Immunology
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Citations in the corpus
- Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes (2018, background): “Signals in the brain environment shape their maturation by driving broad changes in gene transcription, morphology, and cell number (Butovsky et al., 2014; Gosselin et al., 2014; Lavin et al., 2014).”
- Monocyte-Macrophages and T Cells in Atherosclerosis (2017, positive): “Inflammatory Macrophages Drive Atherosclerosis Progression Macrophage functions can vary widely depending on a number of interacting variables and factors, including local environment (‘‘tissue niche’’) (Gosselin et al., 2014; Lavin et al., 2014), intracellular energy metabolism (Van den Bossche et ”
- Dissecting Immune Circuits by Linking CRISPR-Pooled Screens with Single-Cell RNA-Seq. (2016, positive): “The myeloid compartment is composed of environmental plastic cells with functional diversity in both cell state and response (Ginhoux and Jung, 2014; Glass and Natoli, 2016; Gosselin et al., 2014; Lavin et al., 2014, 2015).”