Background: Biliary atresia (BA) is a devastating inflammatory and fibrosing cholangiopathy of neonates with unknown aetiology. We aim to investigate the relationship between these two main characteristics.
Methods: Single-cell RNA sequencing and spatial transcriptomics were performed on liver samples from a cohort of 14 objects (BA: n = 6; control: n = 8). We conducted data integration and cell-type annotation based on gene expression profiling. Furthermore, we identified fibrosis-related immune cells according to their spatial locations, GO and KEGG analysis. Finally, SPOTlight and CIBERSORTx were used to deconvolute ST data and microarray data of the GSE46960 cohorts, respectively.
Results: Immune subpopulations inhabiting the 'fibrotic niche' (areas of scarring), comprising 'intermediate' CD14 CD16 monocytes, scar-associated macrophages, natural killer T cells, transitional B cells and FCN3 neutrophils were identified. GO and KEGG analyses showed that pathways including 'positive regulation of smooth muscle cell/fibroblast proliferation' and 'positive regulation of/response to VEGFR/VEGF/EGFR/FGF' were enriched in these cell types. Interactions analysis showed that communication among 'FGF_FGFR', 'RPS19-C5AR1', 'CD74_COPA/MIF/APP' and 'TNFRSF1A/B_GRN' was extensive. Finally, the results of deconvolution for ST data and microarray data validated that the proportions of certain identified fibrosis-related cell types we identified were increased in BA.
Discussion: Fibrosis is an important feature of BA, in which the immune system plays an important role. Our work reveals the subpopulations of immune cells enriched in the fibrotic niche of BA liver, as well as key related pathways and molecules; some are highlighted for the first time in liver fibrosis. These newly identified interactions might partly explain why the rate of liver fibrosis occurs much faster in BA than in other liver diseases.
Conclusion: Our study revealed the molecular, cellular and spatial immune microenvironment of the fibrotic niche of BA.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636046 | PMC |
| http://dx.doi.org/10.1002/ctm2.1070 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy.
Sci Immunol
January 2025
Irving Institute for Cancer Dynamics, Columbia University, New York, NY 10027, USA.
Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based spatial analysis. In acute myeloid leukemia (AML) DLI responders, we identified clonally expanded CD8 cytotoxic T lymphocytes with in vitro specificity for patient-matched AML.
View Article and Find Full Text PDFRoles of Cellular Neighborhoods in Hepatocellular Carcinoma Pathogenesis.
Annu Rev Pathol
January 2025
Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
The development of hepatocellular carcinoma (HCC) involves an intricate interplay among various cell types within the liver. Unraveling the orchestration of these cells, particularly in the context of various etiologies, may hold the key to deciphering the underlying mechanisms of this complex disease. The advancement of single-cell and spatial technologies has revolutionized our ability to determine cellular neighborhoods and understand their crucial roles in disease pathogenesis.
View Article and Find Full Text PDFResolving spatiotemporal dynamics in bacterial multicellular populations: approaches and challenges.
Microbiol Mol Biol Rev
January 2025
General Microbiology, Technische Universität Dresden, Dresden, Germany.
SUMMARYThe development of multicellularity represents a key evolutionary transition that is crucial for the emergence of complex life forms. Although multicellularity has traditionally been studied in eukaryotes, it originates in prokaryotes. Coordinated aggregation of individual cells within the confines of a colony results in emerging, higher-level functions that benefit the population as a whole.
View Article and Find Full Text PDFDetection of Cancer Stem Cells from Patient Samples.
Cells
January 2025
Institute of Biomedicine and FICAN West Cancer Centre Laboratory, University of Turku and Turku University Hospital, FI-20520 Turku, Finland.
The existence of cancer stem cells (CSCs) in various tumors has become increasingly clear in addition to their prominent role in therapy resistance, metastasis, and recurrence. For early diagnosis, disease progression monitoring, and targeting, there is a high demand for clinical-grade methods for quantitative measurement of CSCs from patient samples. Despite years of active research, standard measurement of CSCs has not yet reached clinical settings, especially in the case of solid tumors.
View Article and Find Full Text PDFExploring the role of metabolic pathways in TNBC immunotherapy: insights from single-cell and spatial transcriptomics.
Front Endocrinol (Lausanne)
January 2025
The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
The article provides an overview of the current understanding of the interplay between metabolic pathways and immune function in the context of triple-negative breast cancer (TNBC). It highlights recent advancements in single-cell and spatial transcriptomics technologies, which have revolutionized the analysis of tumor heterogeneity and the immune microenvironment in TNBC. The review emphasizes the crucial role of metabolic reprogramming in modulating immune cell function, discussing how specific metabolic pathways, such as glycolysis, lipid metabolism, and amino acid metabolism, can directly impact the activity and phenotypes of various immune cell populations within the TNBC tumor microenvironment.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!