Non ‐negative blind deconvolution for signal processing in a CRISPR‐edited iPSC‐cardiomyocyte model of dilated cardiomyopathy

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 wildtype control iPSCs (MUT). The NNDB-based method enabled data parametrization, fitting, and analysis in wildtype 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 development of novel diagnostic tools.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: RESEARCH LETTER Source Type: research