Electrical stimulation applied during differentiation drives the hiPSC-CMs towards a mature cardiac conduction-like cells.
Action Potentials
/ physiology
Biomarkers
/ metabolism
Calcium
/ metabolism
Cell Differentiation
Cell- and Tissue-Based Therapy
/ methods
Connexins
/ genetics
Contactin 2
/ genetics
Electric Stimulation
Gene Expression
Heart Conduction System
/ cytology
Homeobox Protein Nkx-2.5
/ genetics
Homeodomain Proteins
/ genetics
Humans
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
/ genetics
Induced Pluripotent Stem Cells
/ cytology
Muscle Proteins
/ genetics
Myocytes, Cardiac
/ cytology
NAV1.5 Voltage-Gated Sodium Channel
/ genetics
Potassium Channels
/ genetics
Primary Cell Culture
Transcription Factors
/ genetics
Troponin I
/ genetics
beta Catenin
/ genetics
Gap Junction alpha-5 Protein
Differentiation
Electrical stimulation
Human induced pluripotent stem cells derived cardiomyocytes
Maturation
Specialized cardiac conduction cells
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
10 12 2020
10 12 2020
Historique:
received:
04
08
2020
accepted:
07
09
2020
pubmed:
24
9
2020
medline:
19
3
2021
entrez:
23
9
2020
Statut:
ppublish
Résumé
Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) resemble fetal cardiomyocytes and electrical stimulation (ES) has been explored to mature the differentiated cells. Here, we hypothesize that ES applied at the beginning of the differentiation process, triggers both differentiation of the hiPSC-CMs into a specialized conduction system (CS) phenotype and cell maturation. We applied ES for 15 days starting on day 0 of the differentiation process and found an increased expression of transcription factors and proteins associated with the development and function of CS including Irx3, Nkx2.5 and contactin 2, Hcn4 and Scn5a, respectively. We also found activation of intercalated disc proteins (Nrap and β-catenin). We detected ES-induced CM maturation as indicated by increased Tnni1 and Tnni3 expression. Confocal micrographs showed a shift towards expression of the gap junction protein connexin 40 in ES hiPSC-CM compared to the more dominant expression of connexin 43 in controls. Finally, analysis of functional parameters revealed that ES hiPSC-CMs exhibited faster action potential (AP) depolarization, longer intracellular Ca
Identifiants
pubmed: 32962862
pii: S0006-291X(20)31760-5
doi: 10.1016/j.bbrc.2020.09.021
pii:
doi:
Substances chimiques
Biomarkers
0
CNTN2 protein, human
0
CTNNB1 protein, human
0
Connexins
0
Contactin 2
0
HCN4 protein, human
0
Homeobox Protein Nkx-2.5
0
Homeodomain Proteins
0
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
0
IRX3 protein, human
0
Muscle Proteins
0
NAV1.5 Voltage-Gated Sodium Channel
0
NKX2-5 protein, human
0
NRAP protein, human
0
Potassium Channels
0
SCN5A protein, human
0
TNNI1 protein, human
0
TNNI3 protein, human
0
Transcription Factors
0
Troponin I
0
beta Catenin
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
376-382Subventions
Organisme : Medical Research Council
ID : MR/R017050/1
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors confirm that there are no conflicts of interest.