Integrative analysis of bulk and single-nucleus transcriptomes suggests proteostasis- and metabolism-related alterations in the right ventricular outflow tract of non-syndromic Tetralogy of Fallot.
H, W., X, Y., Y, G., W, L., Z, C., Z, L., & W, X. (2026). Integrative analysis of bulk and single-nucleus transcriptomes suggests proteostasis- and metabolism-related alterations in the right ventricular outflow tract of non-syndromic Tetralogy of Fallot.. Functional & integrative genomics. https://doi.org/10.1007/s10142-026-01898-w
H W, X Y, Y G, W L, Z C, Z L, et al. Integrative analysis of bulk and single-nucleus transcriptomes suggests proteostasis- and metabolism-related alterations in the right ventricular outflow tract of non-syndromic Tetralogy of Fallot.. Functional & integrative genomics. 2026; doi: 10.1007/s10142-026-01898-w
H W, X Y, Y G, et al. Integrative analysis of bulk and single-nucleus transcriptomes suggests proteostasis- and metabolism-related alterations in the right ventricular outflow tract of non-syndromic Tetralogy of Fallot.[J]. Functional & integrative genomics. 2026. DOI: 10.1007/s10142-026-01898-w.
@article{h2026,
author = {Wang H and Yong X and Gao Y and Li W and Chen Z and Liu Z and Xu W},
title = {Integrative analysis of bulk and single-nucleus transcriptomes suggests proteostasis- and metabolism-related alterations in the right ventricular outflow tract of non-syndromic Tetralogy of Fallot.},
journal = {Functional & integrative genomics},
year = {2026},
doi = {10.1007/s10142-026-01898-w},
note = {PMID: 42230411},
}
TY - JOUR AU - Wang H AU - Yong X AU - Gao Y AU - Li W AU - Chen Z AU - Liu Z AU - Xu W TI - Integrative analysis of bulk and single-nucleus transcriptomes suggests proteostasis- and metabolism-related alterations in the right ventricular outflow tract of non-syndromic Tetralogy of Fallot. T2 - Functional & integrative genomics PY - 2026 DO - 10.1007/s10142-026-01898-w AN - PMID:42230411 ER -
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, among which non-syndromic TOF (nsTOF) represents the most common subtype; however, the molecular mechanisms underlying right ventricular outflow tract (RVOT) remodeling in nsTOF remain incompletely understood. Bulk transcriptomic and single-nucleus RNA sequencing (snRNA-seq) datasets derived from fetal and infant RVOT tissues were integrated for analysis. Differential expression, miRNA-mRNA regulatory network construction, protein-protein interaction analysis, functional enrichment, and pseudotime trajectory analyses were performed to identify candidate hub genes and dynamic transcriptional alterations associated with nsTOF. A total of 842 differentially expressed mRNAs and 66 differentially expressed miRNAs were identified. Integration analyses yielded a regulatory network containing 54 DE-miRNAs and 538 DE-mRNAs. Fourteen hub genes, including PSMD14, NDUFA5, RPS27L, MRPS16, FOS, and SNRNP70, were identified through consensus topological filtering. Functional analyses suggested potential involvement of pathways related to protein homeostasis, ribosome-associated quality control, RNA splicing, mitochondrial metabolism, and stress-response signaling. snRNA-seq analysis demonstrated cell type-specific expression patterns of hub genes. Pseudotime analysis further suggested stage-dependent transcriptional alterations during RVOT remodeling. Integrated multi-omics analysis identified 14 candidate hub genes potentially involved in RVOT remodeling in nsTOF. These findings suggest that dysregulation of protein homeostasis, RNA-processing pathways, and mitochondrial metabolic processes may contribute to nsTOF pathology. Further experimental validation is required to confirm these observations.