Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27262757", "kind": "science-record", "revision": 4, "content_hash": "sha256:a9aadeea604d4092e6a937e8a78be778160b803362c38a22c13e238a2fc29211", "created_at": "2026-11-01T15:40:18Z", "updated_at": "2026-11-01T21:20:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions.", "doi": "10.1016/j.jhep.2016.05.037", "pmid": "27262757", "authors": ["Lynette Beattie", "Amy Sawtell", "Jason Mann", "Teija C M Frame", "Bianca Teal", "Fabian de Labastida Rivera", "Najmeeyah Brown", "Katherine Walwyn-Brown", "John W J Moore", "Sandy MacDonald", "Eng-Kiat Lim", "Jane E Dalton", "Christian R Engwerda", "Kelli P MacDonald", "Paul M Kaye"], "journal": "Journal of hepatology", "year": 2016, "abstract": "BACKGROUND & AIMS: Kupffer cells (KCs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. Recent studies have identified KCs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. Although it is now established that following local tissue injury, bone marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, the extent to which newly differentiated macrophages functionally resemble the KCs they have replaced has not been extensively studied.\nMETHODS: We studied the two populations of KCs using intravital microscopy, morphometric analysis and gene expression profiling. An ion homeostasis gene signature, including genes associated with scavenger receptor function and extracellular matrix deposition, allowed discrimination between these two KC sub-types.\nRESULTS: Bone marrow derived \"KCs\" accumulating as a result of genotoxic injury, resemble but are not identical to their yolk sac counterparts. Reflecting the differential expression of scavenger receptors, yolk sac-derived KCs were more effective at accumulating acetylated low density lipoprotein, whereas surprisingly, they were poorer than bone marrow-derived KCs when assessed for uptake of a range of bacterial pathogens. The two KC populations were almost indistinguishable in regard to i) response to lipopolysaccharide challenge, ii) phagocytosis of effete red blood cells and iii) their ability to contain infection and direct granuloma formation against Leishmania donovani, a KC-tropic intracellular parasite.\nCONCLUSIONS: Bone marrow-derived KCs differentiate locally to resemble yolk sac-derived KC in most but not all respects, with implications for models of infectious diseases, liver injury and bone marrow transplantation. In addition, the gene signature we describe adds to the tools available for distinguishing KC subpopulations based on their ontology.\nLAY SUMMARY: Liver macrophages play a major role in the control of infections in the liver and in the pathology associated with chronic liver diseases. It was recently shown that liver macrophages can have two different origins, however, the extent to which these populations are functionally distinct remains to be fully addressed. Our study demonstrates that whilst liver macrophages share many features in common, regardless of their origin, some subtle differences in function exist.\nDATA REPOSITORY: Gene expression data are available from the European Bioinformatics Institute ArrayExpress data repository (accession number E-MTAB-4954).", "claims": [{"id": "claim-method", "statement": "Comparison of the gene expression data between liver resident and BM-derived KCs was performed using the Benjamini and Hochberg false discovery rate (FDR) correction [24].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27262757", "locator": "sections[8] \"Whole genome array\" paragraph 2", "quote": "Comparison of the gene expression data between liver resident and BM-derived KCs was performed using the Benjamini and Hochberg false discovery rate (FDR) correction [24]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Gene expression data are available from the European Bioinformatics Institute ArrayExpress data repository (accession number E-MTAB-4954).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27262757", "locator": "sections[0] \"Abstract\" paragraph 7", "quote": "Gene expression data are available from the European Bioinformatics Institute ArrayExpress data repository (accession number E-MTAB-4954)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study used microarray gene-expression profiling analyzed with Benjamini–Hochberg false discovery rate correction at a 5% FDR and a 2-fold expression criterion; the underlying gene-expression data are available from the European Bioinformatics Institute ArrayExpress repository under accession E-MTAB-4954.", "kind": "quantitative", "target": {"value": 2.0, "unit": "fold change", "tolerance": null, "source": "A 2-fold expression criterion was then applied to each gene list."}, "evidence": [{"asset": "source:pmid:27262757", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Bone marrow derived “KCs” accumulating as a result of genotoxic injury, resemble but are not identical to their yolk sac counterparts."}, {"asset": "source:pmid:27262757", "locator": "sections[0] \"Abstract\" paragraph 7", "quote": "Gene expression data are available from the European Bioinformatics Institute ArrayExpress data repository (accession number E-MTAB-4954)."}, {"asset": "source:pmid:27262757", "locator": "sections[8] \"Whole genome array\" paragraph 2", "quote": "Comparison of the gene expression data between liver resident and BM-derived KCs was performed using the Benjamini and Hochberg false discovery rate (FDR) correction [24]."}, {"asset": "source:pmid:27262757", "locator": "sections[8] \"Whole genome array\" paragraph 2", "quote": "This analysis was performed with GeneSpring software (version 9; Agilent) as a standard 5% FDR, with the variances assessed by the software for each t test performed."}, {"asset": "source:pmid:27262757", "locator": "sections[8] \"Whole genome array\" paragraph 2", "quote": "A 2-fold expression criterion was then applied to each gene list."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study used microarray gene-expression profiling analyzed with Benjamini–Hochberg false discovery rate correction at a 5% FDR and a 2-fold expression criterion; the underlying gene-expression data are available from the European Bioinformatics Institute ArrayExpress repository under accession E-MTAB-4954.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:27262757"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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