A single-cell view of biliary atresia

Russi, Abigail E.; Bezerra, Jorge A.

doi:10.1038/s41575-021-00417-5

Cited by 4 publications

(5 citation statements)

References 9 publications

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“…A plethora of proinlammatory immune cells have been shown to contribute to this response either directly through oligoclonal expansion or through the release of cytokines, autoantibodies, and other immune mediators (39). More recent evidence further supports the role of the innate immune system in regulating pathogenic mechanism in BA (40). A novel single cell analysis of liver tissue from infants with BA showed a key role for resident macrophages and other proinlammatory cells in the initial damage to cholangiocytes as well as the progression to liver ibrosis (41).…”

Section: Discussionmentioning

confidence: 96%

“…A novel single cell analysis of liver tissue from infants with BA showed a key role for resident macrophages and other proinflammatory cells in the initial damage to cholangiocytes as well as the progression to liver fibrosis (41). Such macrophages (Kupffer cells) are believed to be pivotal in the secretion of MMP-7 in BA (40,42), and the observed high MMP-7 levels seem to reflect this macrophage-driven fibrogenic process rather than reflecting a more BA-exclusive pathway. This is further supported by the finding that biliary MMP-7 expression (at gene and protein level) shows positive correlation with Metavir fibrosis stage and portal fibrosis grade in BA patients (20).…”

Section: Discussionmentioning

confidence: 99%

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Matrix Metalloproteinase-7 and Osteopontin Serum Levels as Biomarkers for Biliary Atresia

Aldeiri¹,

Si²,

Huang³

et al. 2023

Journal of Pediatric Gastroenterology &Amp; Nutrition

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Objectives: Matrix metallopeptidase-7 (MMP-7) and osteopontin (OPN) are important components in the pathophysiology of fibrosis in biliary atresia (BA). There has been much recent interest in MMP-7 serum level in the diagnosis of BA. We aimed to assess the diagnostic accuracy and prognostic value of both MMP-7 and OPN in a Western BA study. Methods: Diagnostic value was assessed by comparison of serum MMP-7 and OPN levels in infants with BA and age-matched cholestatic controls. Prognostic value was assessed through subsequent clearance of jaundice (COJ) and need for liver transplantation (LT). Results: Serum was assessed from 32 BA and 27 controls. Median MMP-7 was higher in BA (96.4 vs 35 ng/mL; P < 0.0001) with an optimal cut-off value of 69 ng/mL. Sensitivity and specificity was 68% and 93%, respectively [negative predictive value (NPV) = 71%]. Similarly, median OPN was higher in BA (1952 vs 1457 ng/mL; P = 0.0001) and an optimal cut-off of 1611 ng/mL. Sensitivity and specificity was 84% and 78%, respectively (NPV = 81%). MMP-7 level correlated positively with Ishak liver fibrosis score (r = 0.27, P = 0.04). Neither MMP-7 (70 vs 100 ng/mL; P = 0.2) nor OPN (1969 vs 1939 ng/mL; P = 0.3) were predictive of COJ, or need for LT (99 vs 79 ng/mL; P = 0.7, and 1981 vs 1899 ng/mL; P = 0.2), respectively. Conclusions: MMP-7 and OPN may have contributory value in the diagnosis of BA, but remain far of the "gold standard" role. Much more prospective data are required and collaborative multi-center initiatives should be the next logical steps.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-7 and Osteopontin Serum Levels as Biomarkers for Biliary Atresia

Aldeiri¹,

Si²,

Huang³

et al. 2023

Journal of Pediatric Gastroenterology &Amp; Nutrition

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“…Mechanically, lncRNAs, miRNAs, inflammatory cytokines, and transcription factors contribute to abnormal cholangiocyte proliferation. Apart from this, mitophagy, beta-amyloid deposition, and immune cells crosstalk are also involved in the development of BA ( 173 – 175 ).…”

Section: Role Of Immune Cells In Biliary Repair In Cholangiopathiesmentioning

confidence: 99%

Role of Immune Cells in Biliary Repair

et al. 2022

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The biliary system is comprised of cholangiocytes and plays an important role in maintaining liver function. Under normal conditions, cholangiocytes remain in the stationary phase and maintain a very low turnover rate. However, the robust biliary repair is initiated in disease conditions, and different repair mechanisms can be activated depending on the pathological changes. During biliary disease, immune cells including monocytes, lymphocytes, neutrophils, and mast cells are recruited to the liver. The cellular interactions between cholangiocytes and these recruited immune cells as well as hepatic resident immune cells, including Kupffer cells, determine disease outcomes. However, the role of immune cells in the initiation, regulation, and suspension of biliary repair remains elusive. The cellular processes of cholangiocyte proliferation, progenitor cell differentiation, and hepatocyte-cholangiocyte transdifferentiation during biliary diseases are reviewed to manifest the underlying mechanism of biliary repair. Furthermore, the potential role of immune cells in crucial biliary repair mechanisms is highlighted. The mechanisms of biliary repair in immune-mediated cholangiopathies, inherited cholangiopathies, obstructive cholangiopathies, and cholangiocarcinoma are also summarized. Additionally, novel techniques that could clarify the underlying mechanisms of biliary repair are displayed. Collectively, this review aims to deepen the understanding of the mechanisms of biliary repair and contributes potential novel therapeutic methods for treating biliary diseases.

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“…Single-cell transcriptomic analyses created from cells in suspension including single-cell RNA-seq (scRNAseq) or single nucleus RNA-seq (snRNAseq) have provided mechanistic insights into liver disease in scarce clinical specimens at a resolution that was previously not possible 4 – 6 . These techniques have emerged as a valuable tool for the study of discrete cell phenotypes to enhance our understanding of disease states and identify potential therapeutic targets in liver disease.…”

Section: Introductionmentioning

confidence: 99%

Technical optimization of spatially resolved single-cell transcriptomic datasets to study clinical liver disease

Rocque,

Guion,

Singh

et al. 2024

Sci Rep

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Single cell and spatially resolved ‘omic’ techniques have enabled deep characterization of clinical pathologies that remain poorly understood, providing unprecedented insights into molecular mechanisms of disease. However, transcriptomic platforms are costly, limiting sample size, which increases the possibility of pre-analytical variables such as tissue processing and storage procedures impacting RNA quality and downstream analyses. Furthermore, spatial transcriptomics have not yet reached single cell resolution, leading to the development of multiple deconvolution methods to predict individual cell types within each transcriptome ‘spot’ on tissue sections. In this study, we performed spatial transcriptomics and single nucleus RNA sequencing (snRNAseq) on matched specimens from patients with either histologically normal or advanced fibrosis to establish important aspects of tissue handling, data processing, and downstream analyses of biobanked liver samples. We observed that tissue preservation technique impacts transcriptomic data, especially in fibrotic liver. Single cell mapping of the spatial transcriptome using paired snRNAseq data generated a spatially resolved, single cell dataset with 24 unique liver cell phenotypes. We determined that cell–cell interactions predicted using ligand–receptor analysis of snRNAseq data poorly correlated with cellular relationships identified using spatial transcriptomics. Our study provides a framework for generating spatially resolved, single cell datasets to study gene expression and cell–cell interactions in biobanked clinical samples with advanced liver disease.

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A single-cell view of biliary atresia

Cited by 4 publications

References 9 publications

Matrix Metalloproteinase-7 and Osteopontin Serum Levels as Biomarkers for Biliary Atresia

Matrix Metalloproteinase-7 and Osteopontin Serum Levels as Biomarkers for Biliary Atresia

Role of Immune Cells in Biliary Repair

Technical optimization of spatially resolved single-cell transcriptomic datasets to study clinical liver disease

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