Dataset Information

Transcriptional profiling of pediatric cholestatic livers identifies three distinct macrophage populations.

ABSTRACT:

Background & aims

Limited 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.

Methods

We 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.

Results

We 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.

Conclusions

We 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.

SUBMITTER: Taylor SA

PROVIDER: S-EPMC7790256 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Transcriptional profiling of pediatric cholestatic livers identifies three distinct macrophage populations.

Taylor Sarah A SA Chen Shang-Yang SY Gadhvi Gaurav G Feng Liang L Gromer Kyle D KD Abdala-Valencia Hiam H Nam Kiwon K Dominguez Salina T ST Montgomery Anna B AB Reyfman Paul A PA Ostilla Lorena L Wechsler Joshua B JB Cuda Carla M CM Green Richard M RM Perlman Harris H Winter Deborah R DR

PloS one 20210107 1

<h4>Background & aims</h4>Limited 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. ...[more]

PMID: 33411796

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Dataset Information

Transcriptional profiling of pediatric cholestatic livers identifies three distinct macrophage populations.

Background & aims

Methods

Results

Conclusions

Publications

Transcriptional profiling of pediatric cholestatic livers identifies three distinct macrophage populations.

Similar Datasets

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