Research ExplorerPublicationsA critical role of retinoic acid concentration for the induc...

A critical role of retinoic acid concentration for the induction of a fully human-like atrial action potential phenotype in hiPSC-CM

Standard

A critical role of retinoic acid concentration for the induction of a fully human-like atrial action potential phenotype in hiPSC-CM. / Schulz, Carl; Sönmez, Muhammed; Krause, Julia; Schwedhelm, Edzard; Bangfen, Pan; Alihodzic, Dzenefa; Hansen, Arne; Eschenhagen, Thomas; Christ, Torsten.

In: STEM CELL REP, Vol. 18, No. 11, 14.11.2023, p. 2096-2107.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schulz, C, Sönmez, M, Krause, J, Schwedhelm, E, Bangfen, P, Alihodzic, D, Hansen, A, Eschenhagen, T & Christ, T 2023, 'A critical role of retinoic acid concentration for the induction of a fully human-like atrial action potential phenotype in hiPSC-CM', STEM CELL REP, vol. 18, no. 11, pp. 2096-2107. https://doi.org/10.1016/j.stemcr.2023.10.006

APA

Schulz, C., Sönmez, M., Krause, J., Schwedhelm, E., Bangfen, P., Alihodzic, D., Hansen, A., Eschenhagen, T., & Christ, T. (2023). A critical role of retinoic acid concentration for the induction of a fully human-like atrial action potential phenotype in hiPSC-CM. STEM CELL REP, 18(11), 2096-2107. https://doi.org/10.1016/j.stemcr.2023.10.006

Vancouver

Schulz C, Sönmez M, Krause J, Schwedhelm E, Bangfen P, Alihodzic D et al. A critical role of retinoic acid concentration for the induction of a fully human-like atrial action potential phenotype in hiPSC-CM. STEM CELL REP. 2023 Nov 14;18(11):2096-2107. https://doi.org/10.1016/j.stemcr.2023.10.006

Bibtex

@article{864c48c6ba314801b44fa77791c8cde7,
title = "A critical role of retinoic acid concentration for the induction of a fully human-like atrial action potential phenotype in hiPSC-CM",
abstract = "Retinoic acid (RA) induces an atrial phenotype in human induced pluripotent stem cells (hiPSCs), but expression of atrium-selective currents such as the ultrarapid (IKur) and acetylcholine-stimulated K+ current is variable and less than in the 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 μM, respectively. Only 1 μM RA induced enough IKur to fully reproduce human atrial action potential (AP) shape and a robust shortening of APs upon carbachol. We found that sterile filtration caused substantial loss of RA. We conclude that 1 μM RA seems to be 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 the success of atrial differentiation.",
keywords = "Humans, Action Potentials, Induced Pluripotent Stem Cells/metabolism, Atrial Fibrillation/metabolism, Tretinoin/pharmacology, Heart Atria, Phenotype, Myocytes, Cardiac",
author = "Carl Schulz and Muhammed S{\"o}nmez and Julia Krause and Edzard Schwedhelm and Pan Bangfen and Dzenefa Alihodzic and Arne Hansen and Thomas Eschenhagen and Torsten Christ",
note = "Copyright {\textcopyright} 2023 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2023",
month = nov,
day = "14",
doi = "10.1016/j.stemcr.2023.10.006",
language = "English",
volume = "18",
pages = "2096--2107",
journal = "STEM CELL REP",
issn = "2213-6711",
publisher = "Cell Press",
number = "11",

}

RIS

TY - JOUR

T1 - A critical role of retinoic acid concentration for the induction of a fully human-like atrial action potential phenotype in hiPSC-CM

AU - Schulz, Carl

AU - Sönmez, Muhammed

AU - Krause, Julia

AU - Schwedhelm, Edzard

AU - Bangfen, Pan

AU - Alihodzic, Dzenefa

AU - Hansen, Arne

AU - Eschenhagen, Thomas

AU - Christ, Torsten

N1 - Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2023/11/14

Y1 - 2023/11/14

N2 - Retinoic acid (RA) induces an atrial phenotype in human induced pluripotent stem cells (hiPSCs), but expression of atrium-selective currents such as the ultrarapid (IKur) and acetylcholine-stimulated K+ current is variable and less than in the 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 μM, respectively. Only 1 μM RA induced enough IKur to fully reproduce human atrial action potential (AP) shape and a robust shortening of APs upon carbachol. We found that sterile filtration caused substantial loss of RA. We conclude that 1 μM RA seems to be 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 the success of atrial differentiation.

AB - Retinoic acid (RA) induces an atrial phenotype in human induced pluripotent stem cells (hiPSCs), but expression of atrium-selective currents such as the ultrarapid (IKur) and acetylcholine-stimulated K+ current is variable and less than in the 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 μM, respectively. Only 1 μM RA induced enough IKur to fully reproduce human atrial action potential (AP) shape and a robust shortening of APs upon carbachol. We found that sterile filtration caused substantial loss of RA. We conclude that 1 μM RA seems to be 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 the success of atrial differentiation.

KW - Humans

KW - Action Potentials

KW - Induced Pluripotent Stem Cells/metabolism

KW - Atrial Fibrillation/metabolism

KW - Tretinoin/pharmacology

KW - Heart Atria

KW - Phenotype

KW - Myocytes, Cardiac

U2 - 10.1016/j.stemcr.2023.10.006

DO - 10.1016/j.stemcr.2023.10.006

M3 - SCORING: Journal article

C2 - 37922915

VL - 18

SP - 2096

EP - 2107

JO - STEM CELL REP

JF - STEM CELL REP

SN - 2213-6711

IS - 11

ER -