ArticleDevelopmental cell2021
Modeling Human TBX5 Haploinsufficiency Predicts Regulatory Networks for Congenital Heart Disease.
Article in Developmental cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 126 citations in OpenAlex.
- Combined effects of maternal periconceptional environmental exposures and infant cardiac transcription factor polymorphisms on congenital heart disease risk.Annals of medicine · 2026Article
- Dose-dependent sensitivity of human three-dimensional chromatin to a heart disease-linked transcription factor.Science (New York, N.Y.) · 2026Article
- Scaling and quantization of large-scale foundation model enables resource-efficient predictions in network biology.Nature computational science · 2026Article
- Enhancer Dynamics for Gene Regulation in the Cardiovascular System.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Paired single-cell imaging of calcium and expression to map niches of identity and function.bioRxiv : the preprint server for biology · 2026Article
- Reduced TBX5 dosage undermines developmental control of atrial cardiomyocyte identity in a model of human atrial disease.Development (Cambridge, England) · 2026Article
- Comprehensive perturbation of transcription factors in human cardiomyocytes reveals the regulatory architecture of congenital heart disease.bioRxiv : the preprint server for biology · 2026Article
- A disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects.Nature cardiovascular research · 2026Article
- Article
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- Modeling rare genetic disease with gene-edited induced pluripotent stem cells: relevance of the starting stock line.Stem cells translational medicine · 2025Article
- Article
- Procollagen IIA mediates positive feedback control of the mouse cardiogenic transcriptional network.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Single-nuclei multiomics analysis identifies abnormal cardiomyocytes in a murine model of cardiac development.Nature communications · 2025Article
- Post-translational modification of transcription factors: perspectives in vascular medicine.Cell death & disease · 2025Review
- Single cell transcriptomics in a treatment-segregated cohort exposes a STAT3-regulated therapeutic gap in idiopathic pulmonary fibrosis.bioRxiv : the preprint server for biology · 2025Article
- Current and future diagnostics of congenital heart disease (CHD).Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Detailed phenotyping of Tbr1-2A-CreER knock-in mice demonstrates significant impacts on TBR1 protein levels and axon development.Autism research : official journal of the International Society for Autism Research · 2025Article
- Polydactyly and syndactyly linked to GLI3 and TBX5 mutations: A pediatric case report.Global medical genetics · 2025Article
- Applications of Single-Cell Omics Technologies for Induced Pluripotent Stem Cell-Based Cardiovascular Research.International journal of stem cells · 2025Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
27 authors at 8 institutions in 2 countries.
Funding
Abstract
Haploinsufficiency of transcriptional regulators causes human congenital heart disease (CHD); however, the underlying CHD gene regulatory network (GRN) imbalances are unknown. Here, we define transcriptional consequences of reduced dosage of the CHD transcription factor, TBX5, in individual cells during cardiomyocyte differentiation from human induced pluripotent stem cells (iPSCs). We discovered highly sensitive dysregulation of TBX5-dependent pathways-including lineage decisions and genes associated with heart development, cardiomyocyte function, and CHD genetics-in discrete subpopulations of cardiomyocytes. Spatial transcriptomic mapping revealed chamber-restricted expression for many TBX5-sensitive transcripts. GRN analysis indicated that cardiac network stability, including vulnerable CHD-linked nodes, is sensitive to TBX5 dosage. A GRN-predicted genetic interaction between Tbx5 and Mef2c, manifesting as ventricular septation defects, was validated in mice. These results demonstrate exquisite and diverse sensitivity to TBX5 dosage in heterogeneous subsets of iPSC-derived cardiomyocytes and predicts candidate GRNs for human CHDs, with implications for quantitative transcriptional regulation in disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.