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Series GSE248029 Query DataSets for GSE248029
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
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.
 
Overall design Hi-C was performed on isolated tissue resident macrophages alter IL-4 treatment in vivo.
 
Contributor(s) Zhao M, Hornick K, Lack J, Link V, Belkaid Y, Jankovic D, Loke P
Citation(s) 38712032
Submission date Nov 16, 2023
Last update date Sep 29, 2024
Contact name Mingming Zhao
E-mail(s) mingming.zhao@nih.gov
Organization name national institutes of health
Street address 9000 Rockville Pike
City Bethesda
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM7904886 BL6_IL4
GSM7904887 BALBc_IL4
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
Relations
BioProject PRJNA1041430

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Supplementary file Size Download File type/resource
GSE248029_RAW.tar 7.4 Gb (http)(custom) TAR (of HIC)
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Raw data are available in SRA

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