Cardiac differentiation roadmap for analysis of plasticity and balanced lineage commitment

Rebecca R. Snabel, Carla Cofiño-Fabrés, Marijke Baltissen, Verena Schwach, Robert Passier*, Gert Jan C. Veenstra*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Stem cell-based models of human heart tissue and cardiac differentiation employ monolayer and 3D organoid cultures with different properties, cell type composition, and maturity. Here we show how cardiac monolayer, embryoid body, and engineered heart tissue trajectories compare in a single-cell roadmap of atrial and ventricular differentiation conditions. Using a multiomic approach and gene-regulatory network inference, we identified regulators of the epicardial, atrial, and ventricular cardiomyocyte lineages. We identified ZNF711 as a regulatory switch and safeguard for cardiomyocyte commitment. We show that ZNF711 ablation prevents cardiomyocyte differentiation in the absence of retinoic acid, causing progenitors to be diverted more prominently to epicardial and other lineages. Retinoic acid rescues this shift in lineage commitment and promotes atrial cardiomyocyte differentiation by regulation of shared and complementary target genes, showing interplay between ZNF711 and retinoic acid in cardiac lineage commitment.

Original languageEnglish
Article number102422
Number of pages18
JournalStem cell reports
Volume20
Issue number3
DOIs
Publication statusPublished - 27 Feb 2025

Keywords

  • UT-Gold-D
  • epicardial cells
  • gene-regulatory networks
  • heart fields
  • human pluripotent stem cells
  • retinoic acid
  • single-cell multiomics
  • ZNF711
  • cardiac lineage commitment

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