Related Experiment Video
Updated: Aug 10, 2026
Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles
Published on: October 15, 2014
A single-cell and spatial transcriptomic atlas of human tuberculous constrictive pericardium
Feng Xiong1, Yangran Qi2, Shuzhen Wang1
1Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, 610031, Sichuan, China.
Background:
Tuberculous pericarditis (TP) can progress to tuberculous constrictive pericarditis (TB-CP), a life-threatening fibrotic syndrome. However, the cellular architecture and intercellular circuits that link granulomatous inflammation to pericardial fibrosis remain poorly defined.
Methods:
We performed single-cell RNA sequencing (scRNA-seq) on 81,634 cells from surgically resected pericardium of six patients with TB-CP and three normal controls. Ligand-receptor and trajectory analyses were integrated with spatial transcriptomics, histology, immunohistochemistry, and multiplex immunofluorescence to map cell states, signalling pathways, and immune-stromal niches in situ.
Findings:
We generated an integrated single-cell and spatial atlas of the human pericardium in TB-CP, delineating 14 major cell types and heterogeneous transcriptional programmes associated with granuloma formation, vascular remodelling, and fibrotic activation. Spatial mapping revealed MMP9+ macrophage-rich granulomatous cores surrounded by infiltrating CCL19+ fibroblasts and T cells. In parallel, S100A4+ endothelial cells displayed endothelial-to-mesenchymal transition-like programmes and trajectories converging on ACTA2+ myofibroblasts, supported by immune cell-derived TGF-β and VEGF signalling. Ligand-receptor analysis and spatial co-localisation suggested macrophages may act as hubs that couple immune activation to endothelial reprogramming, fibroblast activation, and T-cell recruitment within fibrotic lesions.
Interpretation:
This human atlas defines the cellular landscape and key intercellular circuits underlying the immunopathogenesis of TB-CP. Our findings show that a spatially organised immune-endothelial-fibroblast network is associated with pericardial fibrosis and nominate VEGF/TGF-β pathways and associated cell states as potential biomarkers and therapeutic targets.
Funding:
National Natural Science Foundation of China (82270486 to F.X.); Science and Technology Bureau of Sichuan Province (2021YFS0051, 2024YFFK0209 to Y.W.; 2024NSFC0646 to F.X.).
