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Periportal macrophages protect against commensal-driven liver inflammation [spatial transcriptomics]

ABSTRACT: Periportal macrophages protect against commensal-driven liver inflammation [spatial transcriptomics]

PROVIDER: PRJNA880838 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21584454_1.fastq.gz	Fastqsanger.gz
	SRR21584454_2.fastq.gz	Fastqsanger.gz
	SRR21584456_1.fastq.gz	Fastqsanger.gz
	SRR21584456_2.fastq.gz	Fastqsanger.gz
	SRR21584457_1.fastq.gz	Fastqsanger.gz

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Periportal macrophages protect against commensal-driven liver inflammation

Project description:Periportal macrophages protect against commensal-driven liver inflammation

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Periportal macrophages protect against commensal-driven liver inflammation [spatial transcriptomics]

Project description: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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Project description:Hepatocytes perform different metabolic functions depending on their proximity to the portal triad (periportal) or central vein (perivenous) in the liver lobule. To improve our understanding of the spatial and functional heterogeneity of hepatocytes, we used single cell RNA sequencing (scRNA-seq) and a novel bioinformatics method, Wave-Crest, to reorder hepatocytes along the periportal to perivenous axis. After isolating hepatocytes from an 8-week old male C57BL/6 mouse, performing scRNA-seq, and reordering the cells along the periportal to perivenous axis, Wave-Crest allowed us to identify novel genes differentially expressed along the axis. Using immunocytochemistry, we verified that select novel genes were expressed in the spatial pattern predicted by Wave-Crest. Hence, our study demonstrates a new approach for recovering spatial information from scRNA-seq data.

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