TY - JOUR
T1 - Cardiac differentiation roadmap for analysis of plasticity and balanced lineage commitment
AU - Snabel, Rebecca R.
AU - Cofiño-Fabrés, Carla
AU - Baltissen, Marijke
AU - Schwach, Verena
AU - Passier, Robert
AU - Veenstra, Gert Jan C.
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025/2/27
Y1 - 2025/2/27
N2 - 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.
AB - 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.
KW - UT-Gold-D
KW - epicardial cells
KW - gene-regulatory networks
KW - heart fields
KW - human pluripotent stem cells
KW - retinoic acid
KW - single-cell multiomics
KW - ZNF711
KW - cardiac lineage commitment
UR - http://www.scopus.com/inward/record.url?scp=86000362346&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2025.102422
DO - 10.1016/j.stemcr.2025.102422
M3 - Article
C2 - 40020683
AN - SCOPUS:86000362346
SN - 2213-6711
VL - 20
JO - Stem cell reports
JF - Stem cell reports
IS - 3
M1 - 102422
ER -