ArticlePloS one2021
Transcriptional profiling of pediatric cholestatic livers identifies three distinct macrophage populations.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Spatial transcriptomics supports a role for SOX4-driven signaling throughout the disease course of biliary atresia.Hepatology communications · 2026Article
- Scar-associated macrophages and biliary epithelial cells interaction exacerbates hepatic fibrosis in biliary atresia.Pediatric research · 2026Article
- Conserved Ductular Reaction Mechanisms in Biliary Atresia and Primary Sclerosing Cholangitis Derived From Single-Cell and Spatial Transcriptomics.Cellular and molecular gastroenterology and hepatology · 2026Review
- Towards a reference cell atlas of liver diversity over the human lifespan.Nature reviews. Gastroenterology & hepatology · 2026Review
- Nicheformer: a foundation model for single-cell and spatial omics.Nature methods · 2025Article
- Increased serum GM-CSF at diagnosis of biliary atresia is associated with improved biliary drainage.Pediatric research · 2025Article
- Transcriptional analysis of murine biliary atresia identifies macrophage heterogeneity and subset-specific macrophage functions.Frontiers in immunology · 2025Article
- Immunology of Biliary Atresia.Seminars in pediatric surgery · 2024Review
- Biliary atresia.Nature reviews. Disease primers · 2024Review
- Dual Deletion ofInternational journal of molecular sciences · 2024Article
- Liver Macrophage Diversity in Health and Disease.Results and problems in cell differentiation · 2024Review
- Deconvolution analysis identified altered hepatic cell landscape in primary sclerosing cholangitis and primary biliary cholangitis.Frontiers in medicine · 2024Article
- NR4A1 deletion promotes pro-angiogenic polarization of macrophages derived from classical monocytes in a mouse model of neovascular age-related macular degeneration.Journal of neuroinflammation · 2023Article
- Single-cell sequencing of a novel model of neonatal bile duct ligation in mice identifies macrophage heterogeneity in obstructive cholestasis.Scientific reports · 2023Article
- CD11c+ macrophages are proangiogenic and necessary for experimental choroidal neovascularization.JCI insight · 2023Article
- Necroptosis of macrophage is a key pathological feature in biliary atresia via GDCA/S1PR2/ZBP1/p-MLKL axis.Cell death & disease · 2023Article
- The Role of Inflammation in Cholestatic Liver Injury.Journal of inflammation research · 2023Review
- Immunobiology of the biliary tract system.Journal of hepatology · 2022Review
- Unraveling the Complexity of Liver Disease One Cell at a Time.Seminars in liver disease · 2022Review
- Biliary Atresia in Children: Update on Disease Mechanism, Therapies, and Patient Outcomes.Clinics in liver disease · 2022Review
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsLimited understanding of the role for specific macrophage subsets in the pathogenesis of cholestatic liver injury is a barrier to advancing medical therapy. Macrophages have previously been implicated in both the mal-adaptive and protective responses in obstructive cholestasis. Recently two macrophage subsets were identified in non-diseased human liver; however, no studies to date fully define the heterogeneous macrophage subsets during the pathogenesis of cholestasis. Here, we aim to further characterize the transcriptional profile of macrophages in pediatric cholestatic liver disease.
methodsWe isolated live hepatic immune cells from patients with biliary atresia (BA), Alagille syndrome (ALGS), and non-cholestatic pediatric liver by fluorescence activated cell sorting. Through single-cell RNA sequencing analysis and immunofluorescence, we characterized cholestatic macrophages. We next compared the transcriptional profile of pediatric cholestatic and non-cholestatic macrophage populations to previously published data on normal adult hepatic macrophages.
resultsWe identified 3 distinct macrophage populations across cholestatic liver samples and annotated them as lipid-associated macrophages, monocyte-like macrophages, and adaptive macrophages based on their transcriptional profile. Immunofluorescence of liver tissue using markers for each subset confirmed their presence across BA (n = 6) and ALGS (n = 6) patients. Cholestatic macrophages demonstrated reduced expression of immune regulatory genes as compared to normal hepatic macrophages and were distinct from macrophage populations defined in either healthy adult or pediatric non-cholestatic liver.
conclusionsWe are the first to perform single-cell RNA sequencing on human pediatric cholestatic liver and identified three macrophage subsets with distinct transcriptional signatures from healthy liver macrophages. Further analyses will identify similarities and differences in these macrophage sub-populations across etiologies of cholestatic liver disease. Taken together, these findings may allow for future development of targeted therapeutic strategies to reprogram macrophages to an immune regulatory phenotype and reduce cholestatic liver injury.
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