Advancing physiological maturation in human induced pluripotent stem cell-derived cardiac muscle by gene editing an inducible adult troponin isoform switch.
TNNI
cardiac
gene editing
induced pluripotent stem cells
myocardial contraction
myocytes
Journal
Stem cells (Dayton, Ohio)
ISSN: 1549-4918
Titre abrégé: Stem Cells
Pays: England
ID NLM: 9304532
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
16
01
2020
accepted:
11
05
2020
pubmed:
5
6
2020
medline:
7
7
2021
entrez:
5
6
2020
Statut:
ppublish
Résumé
Advancing maturation of stem cell-derived cardiac muscle represents a major barrier to progress in cardiac regenerative medicine. Cardiac muscle maturation involves a myriad of gene, protein, and cell-based transitions, spanning across all aspects of cardiac muscle form and function. We focused here on a key developmentally controlled transition in the cardiac sarcomere, the functional unit of the heart. Using a gene-editing platform, human induced pluripotent stem cell (hiPSCs) were engineered with a drug-inducible expression cassette driving the adult cardiac troponin I (cTnI) regulatory isoform, a transition shown to be a rate-limiting step in advancing sarcomeric maturation of hiPSC cardiac muscle (hiPSC-CM) toward the adult state. Findings show that induction of the adult cTnI isoform resulted in the physiological acquisition of adult-like cardiac contractile function in hiPSC-CMs in vitro. Specifically, cTnI induction accelerated relaxation kinetics at baseline conditions, a result independent of alterations in the kinetics of the intracellular Ca
Identifiants
pubmed: 32497296
doi: 10.1002/stem.3235
pmc: PMC7529900
mid: NIHMS1608958
doi:
Substances chimiques
Protein Isoforms
0
Troponin I
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1254-1266Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL132874
Pays : United States
Informations de copyright
©AlphaMed Press 2020.
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