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| Status |
Public on Aug 10, 2023 |
| Title |
Discrimination of cell-intrinsic and environment-dependent effects of natural genetic variation on Kupffer cell epigenomes and transcriptomes [ChIP] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Noncoding genetic variation is a major driver of phenotypic diversity but determining the underlying mechanisms and the cell types in which it acts remain challenging problems. Here, we investigate the impact of natural genetic variation provided by phenotypically diverse inbred strains of mice on gene expression and epigenetic landscapes of Kupffer cells. Analysis of gene expression in Kupffer cells and other liver cell types derived from C57BL/6J, BALB/cJ and A/J mice provided evidence for strain-specific differences in environmental factors influencing Kupffer cell phenotypes, including preferential Leptin signaling in BALB/cJ Kupffer cells. Systematic analysis of transcriptomic and epigenetic data from F1 hybrids of these mice, and transcriptomic data from strain-specific Kupffer cells engrafted into a common host enabled quantitative assessment of cis versus trans effects of genetic variation on gene expression and an estimate of cell autonomous versus non cell autonomous effects. Under homeostatic conditions, trans effects of genetic variation were dominant, with the majority of trans regulation being non cell autonomous. In contrast, strain specific responses to acutely administered LPS were primarily associated with genetic variation acting in cis to modify response elements for lineage determining and signal dependent transcription factors. Collectively, these findings reveal cell intrinsic and environmental effects of natural genetic variation on gene expression, demonstrate the use of enhancers as detectors of trans effects of genetic variation, and provide a new resource for understanding the impact of genetic variation on gene expression in Kupffer cells.
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| Overall design |
RNA-seq of hepatic cells and BMDMs from three strains of mice (A/J, BALB/cJ, and C57BL/6J). RNA-seq of Kupffer cells in each strain after 30 minutes of AMLN control diet. RNA-seq from Kupffer cells derived from CB6F1/J hybrid mice and Nod-Scid mice transplanted with C57BL/6J or BALB/cJ bone marrow. RNA-seq and ATAC-seq from C57BL/6J, BALB/cJ, and CB6F1/J Kupffer cells and BMDMs treated with LPS. ATAC-seq and H3K27Ac ChIP-seq from Kupffer cells derived from A/J, BALB/cJ, C57BL/6J, and CB6F1/J mice.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/37735593/
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| Contributor(s) |
Glass CK |
| Citation(s) |
37735593 |
| |
| Submission date |
Oct 19, 2022 |
| Last update date |
Nov 21, 2023 |
| Contact name |
Hunter Bennett |
| E-mail(s) |
h1bennet@health.ucsd.edu
|
| Phone |
3603031396
|
| Organization name |
University of California, San Diego
|
| Department |
Dept. of Cellular & Molecular Medicine
|
| Lab |
Christopher K. Glass Laboratory
|
| Street address |
9500 Gilman Drive, MC 0651
|
| City |
La Jolla |
| State/province |
California |
| ZIP/Postal code |
92093 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (22)
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| This SubSeries is part of SuperSeries: |
| GSE216164 |
Discrimination of cell-intrinsic and environment-dependent effects of natural genetic variation on Kupffer cell epigenomes and transcriptomes |
|
| Relations |
| BioProject |
PRJNA892108 |
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