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Status |
Public on Dec 29, 2023 |
Title |
Genetic variation in IL-4 activated tissue resident macrophages alters the epigenetic state to determine strain specific synergistic responses to LPS [Hi-C] |
Organism |
Mus musculus |
Experiment type |
Other
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Summary |
IL-4 activates tissue resident macrophages (TRMs) to mediate tissue repair and clearance of nematode infections in mice, but most studies have been performed on the C57BL/6 background. The natural genetic variation between C57BL/6 and BALB/c mouse strains can result in differences in allergic responses, parasite resistance, monocyte to macrophage conversion and response to IL-4 activation. Here, we investigated in vivo IL-4 activation in TRMs of the peritoneal cavity from C57BL/6 and BALB/c mice and find that C57BL/6 TRMs are surprisingly more transcriptionally responsive to IL-4 stimulation, with greater association of induced genes with super enhancers, induced enhancers and topologically associating domains (TAD) boundaries. IL-4-directed epigenomic remodeling showed NF-κB motif enrichment only in C57BL/6 TRMs. This resulted in an enhanced synergistic response upon in vitro lipopolysaccharide (LPS) exposure in IL-4 activated C57BL/6 TRMs but not for BALB/c, despite unstimulated BALB/c TRMs having a stronger transcriptional response to LPS than C57BL/6 TRMs. Single cell RNA sequencing (scRNAseq) analysis of mixed bone marrow chimeric mice indicates that transcriptional differences between C57BL/6 and BALB/c TRMs is cell intrinsic within the same tissue environment. Hence, genetic variation alters IL-4-induced cell intrinsic epigenetic reprogramming between C57BL/6 and BALB/c TRMs to regulate the magnitude of synergistic responses to LPS exposure.
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Overall design |
Hi-C was performed on isolated tissue resident macrophages alter IL-4 treatment in vivo.
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Contributor(s) |
Zhao M, Hornick K, Lack J, Link V, Belkaid Y, Jankovic D, Loke P |
Citation(s) |
38712032 |
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Submission date |
Nov 16, 2023 |
Last update date |
Sep 29, 2024 |
Contact name |
Mingming Zhao |
E-mail(s) |
mingming.zhao@nih.gov
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Organization name |
national institutes of health
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Street address |
9000 Rockville Pike
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City |
Bethesda |
ZIP/Postal code |
20892 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (2) |
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This SubSeries is part of SuperSeries: |
GSE248038 |
Genetic variation in IL-4 activated tissue resident macrophages alters the epigenetic state to determine strain specific synergistic responses to LPS |
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Relations |
BioProject |
PRJNA1041430 |