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Updated: Jul 16, 2026
Isolation of Murine Valve Endothelial Cells
Published on: August 21, 2014
Single-Cell Transcriptomics Identified Fibrosis-Activated Valve Interstitial Cells Involved in Functional Tricuspid
Ruojin Zhao1, Mengxia Fu2, Songren Shu3
1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
The treatment of functional tricuspid regurgitation (TR) is still controversial. Characterizing the cellular composition of the tricuspid valve and identifying the molecular alterations of each cell type in valves with TR will advance our understanding of the mechanisms of TR and guide improvements in treatment.
Objectives:
The authors aimed to investigate the changes in cellular composition and gene expression patterns of cells in regurgitant tricuspid valves and shed light on the mechanisms of functional TR.
Methods:
To improve our understanding of the pathogenesis of functional TR, we performed single-cell RNA sequencing of tricuspid valve from 10 patients, including 5 patients with moderate-to-severe functional TR and 5 nondiseased control subjects. Multiplexed fluorescence was used to detect the spatial distributions of valvular cell states and validated the cell-cell interaction.
Results:
We assessed the transcriptional profiles of 84,102 cells and identified 6 major cell clusters, along with 25 cell subtypes, in the specimens. Valve interstitial cells (VICs) were the largest population. VICs and lymphoid cells exhibited more heterogeneity in TR patients. VICs exhibited higher transcriptional activity toward matrifibrocyte-like cells and myofibroblast-like cell differentiation, myeloid cells activated immune response, and lymphoid cells promoted fibrosis. In TR, the alternation of COMP-CD47 and FGF2-FGFR1 interaction may occur in TR specimens, which may serve as promising therapeutic targets for TR.
Conclusions:
Our single-cell atlas highlights the transcriptomic heterogeneity underlying the cell functions and interactions in human tricuspid valves and defines molecular and cellular perturbations in functional TR. We identified VIC clusters with fibrosis activation accumulated in TR valves.
