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| Status |
Public on Mar 06, 2024 |
| Title |
Periportal macrophages protect against commensal-driven liver inflammation [spatial transcriptomics] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The liver is the main gateway from the gut and the unidirectional sinusoidal flow from portal to central veins constitutes heterogenous zonation, such as peri-portal vein (PV) and peri-central vein (CV) zones; however, the functional and molecular differences among liver macrophages in these zones remain poorly understood. Here, intravital multiphoton imaging revealed significantly suppressed in PV zones. Zonation-specific single-cell transcriptome analyses detected an immuno-suppressive macrophage subset highly expressing IL-10 and Marco, a scavenger receptor, enriched in PV zones. Inhibited IL-10 signaling and Marco-deficient conditions impaired the suppressive function of these macrophages. The reduced number of Marco-positive suppressive macrophages in germ-free or antibiotic-treated conditions suggested that gut commensal bacteria were responsible for inducing this specific population. Dextran sulfate sodium-induced colitis led to inflammation in liver PV zones, which was more prominent under Marco-deficient conditions. Marco-positive inflammatory macrophages in the human liver are diminished in primary sclerosing cholangitis (PSC), an intractable disease characterized by chronic inflammation around the portal veins and bile ducts. Collectively, commensal bacteria and their pathogenic substances induce Marco-positive immunosuppressive macrophages, consequently limiting excessive inflammation in PV zones. Failure of this self-limiting system may cause hepatic inflammatory disorders, such as PSC.
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| Overall design |
Spatial transcriptome analysis on the healthy mouse liver using 10X Visium
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| Contributor(s) |
Miyamoto Y, Okuzaki D, Ishii M |
| Citation(s) |
38658756 |
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| Submission date |
Sep 14, 2022 |
| Last update date |
Jul 01, 2024 |
| Contact name |
Daisuke Motooka |
| E-mail(s) |
dry_team@ngs.gen-info.osaka-u.ac.jp
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| Organization name |
NGS core facility, Research Institute for Microbial Diseases, Osaka University
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| Street address |
3-1, Yamadaoka
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| City |
Suita |
| State/province |
Osaka |
| ZIP/Postal code |
5650871 |
| Country |
Japan |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA880838 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE213388_RAW.tar |
272.5 Mb |
(http)(custom) |
TAR (of CSV, JPG, MTX, PNG, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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