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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 [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| 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 |
8 samples were anlysied (Ctrl and IL4 treatment in each strain, 2 replicates per samples)
UPDATE: [09-30-2024] The GSM7904801_BL6_Ctrl_1.genrich.RPM.bw file was renamed to GSM7904804_BL6_IL4_2.genrich.RPM.bw, and vice versa.
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| Contributor(s) |
Zhao M, Link V, Hornick K, Lack J, Belkaid Y, Jankovic D, Loke P |
| Citation(s) |
38712032, 39863579 |
| |
| Submission date |
Nov 16, 2023 |
| Last update date |
Mar 27, 2025 |
| 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 |
| |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL30172 |
NextSeq 2000 (Mus musculus) |
|
| Samples (16)
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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 |
|
| Relations |
| BioProject |
PRJNA1041416 |
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