A critical role of retinoic acid concentration for the induction of a fully human-like atrial phenotype in hiPSC-CM
Schulz, C.; Soenmez, M.; Krause, J.; Schwedhelm, E.; Bangfen, P.; Alihodzic, D.; Hansen, A.; Eschenhagen, T.; Christ, T.
Show abstract
Retinoic acid (RA) induces an atrial phenotype in human induced pluripotent stem cells (hiPSC), but expression of atrium-selective currents such as the ultrarapid (IKur) and acetylcholine-stimulated K+ current (IK,ACh) is variable and less than in adult human atrium. We suspected methodological issues and systematically investigated the concentration-dependency of RA. RA treatment increased IKur concentration-dependently from 1.1{+/-}0.54 pA/pF (0 RA) to 3.8{+/-}1.1, 5.8{+/-}2.5 and 12.2{+/-}4.3 at 0.01, 0.1 and 1 {micro}M, respectively. Only 1 {micro}M RA induced enough IKur to fully reproduce human atrial AP shape and a robust shortening of action potentials (AP) upon carbachol. We found that sterile filtration caused substantial loss of RA. We conclude that 1 {micro}M RA appears necessary and sufficient to induce a full atrial AP shape in hiPSC-CM in EHT format. RA concentrations are prone to methodological issues and may profoundly impact success of atrial differentiation.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Human iPSC-Based Model Reveals NOX4 as Therapeutic Target in Duchenne Cardiomyopathy 91%
- The Aryl Hydrocarbon Receptor Promotes Differentiation During Mouse Preimplantational Embryo Development 90%
- Impulse initiation in engrafted pluripotent stem cell-derived cardiomyocytes can stimulate the recipient heart. 90%
Similar papers in this journal
- Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes 92%
- The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice 92%
- Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts 92%
Similar papers in this journal
- Advanced Cardiac Organoid Model for Studying Doxorubicin-Induced Cardiotoxicity 94%
- Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes 92%
- Bisphenol S and bisphenol F are less disruptive to cardiac electrophysiology and potentially safer for use in medical products, as compared to bisphenol A 89%
Similar papers in this journal
- Remodelling of potassium currents underlies arrhythmic action potential prolongation under beta-adrenergic stimulation in hypertrophic cardiomyopathy 93%
- Development and Characterization of the Mode-of-Action of Inhibitory and Agonist Peptides Targeting the Voltage-Gated Sodium Channel SCN1B/β1 Subunit 92%
- Age-related structural and functional changes of the intracardiac nervous system 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.