Non-negative blind deconvolution for signal processing in a CRISPR-edited iPSC-cardiomyocyte model of dilated cardiomyopathy.
FEBS Lett
; 595(20): 2544-2557, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-34482543
ABSTRACT
We developed an integrated platform for analysis of parameterized data from human disease models. We report a non-negative blind deconvolution (NNBD) approach to quantify calcium (Ca2+ ) handling, beating force and contractility in human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) at the single-cell level. We employed CRISPR/Cas gene editing to introduce a dilated cardiomyopathy (DCM)-causing mutation in troponin T (TnT), TnT-R141W, into wild-type control iPSCs (MUT). The NNDB-based method enabled data parametrization, fitting and analysis in wild-type controls versus isogenic MUT iPSC-CMs. Of note, Cas9-edited TnT-R141W iPSC-CMs revealed significantly reduced beating force and prolonged contractile event duration. The NNBD-based platform provides an alternative framework for improved quantitation of molecular disease phenotypes and may contribute to the development of novel diagnostic tools.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Dilatada
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Miócitos Cardíacos
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Células-Tronco Pluripotentes Induzidas
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Sistemas CRISPR-Cas
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Edição de Genes
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Modelos Biológicos
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article