ArticleCell genomics2024
Single-cell multi-modal integrative analyses highlight functional dynamic gene regulatory networks directing human cardiac development.
Article in Cell genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Benchmarking and optimizing Perturb-seq in differentiating human pluripotent stem cells.Stem cell reports · 2025Article
- Editing stem cell genomes at scale to measure variant effects in diverse cell and genetic contexts.medRxiv : the preprint server for health sciences · 2025Article
- Integrating Spatial Omics and Deep Learning: Toward Predictive Models of Cardiomyocyte Differentiation Efficiency.Bioengineering (Basel, Switzerland) · 2025Review
- Single-nuclei multiomics analysis identifies abnormal cardiomyocytes in a murine model of cardiac development.Nature communications · 2025Article
- Patterning Defects in Mice with Defective Ventricular Wall Maturation and Cardiomyopathy.Journal of cardiovascular development and disease · 2025Article
- Dissecting cardiovascular disease-associated noncoding genetic variants using human iPSC models.Stem cell reports · 2025Review
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Authors and funding
8 authors.
Funding
Abstract
Illuminating the precise stepwise genetic programs directing cardiac development provides insights into the mechanisms of congenital heart disease and strategies for cardiac regenerative therapies. Here, we integrate in vitro and in vivo human single-cell multi-omic studies with high-throughput functional genomic screening to reveal dynamic, cardiac-specific gene regulatory networks (GRNs) and transcriptional regulators during human cardiomyocyte development. Interrogating developmental trajectories reconstructed from single-cell data unexpectedly reveal divergent cardiomyocyte lineages with distinct gene programs based on developmental signaling pathways. High-throughput functional genomic screens identify key transcription factors from inferred GRNs that are functionally relevant for cardiomyocyte lineages derived from each pathway. Notably, we discover a critical heat shock transcription factor 1 (HSF1)-mediated cardiometabolic GRN controlling cardiac mitochondrial/metabolic function and cell survival, also observed in fetal human cardiomyocytes. Overall, these multi-modal genomic studies enable the systematic discovery and validation of coordinated GRNs and transcriptional regulators controlling the development of distinct human cardiomyocyte populations.
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