Paradoxical effects of ZIM3, a CRISPRi effector, on human induced pluripotent stem-cell-derived cardiomyocyte electrophysiology

Paradoxical effects of ZIM3, a CRISPRi effector, on human induced pluripotent stem-cell-derived cardiomyocyte electrophysiology

We show that zinc finger imprinted 3 (Zim3), when used as Zim3-KRAB-dCas9 effector in interference CRISPR, without any guide RNAs, paradoxically up-regulates key cardiac ion channel genes in human-induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs), responsible for healthy resting membra...

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Veröffentlicht in:PNAS nexus 2024-03, Vol.3 (3), p.pgae027-pgae027
Hauptverfasser: Han, Julie L, Heinson, Yuli W, Pozo, Maria R, Li, Weizhen, Entcheva, Emilia
Format: Artikel
Sprache:eng
Schlagworte:
Brief Report
Chromatin
DNA binding proteins
Electric properties
Gene expression
Genes
Genetic aspects
Genetic transcription
Heart
Heart cells
Muscles
Physiological aspects
RNA sequencing
Stem cells
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Beschreibung
Zusammenfassung:We show that zinc finger imprinted 3 (Zim3), when used as Zim3-KRAB-dCas9 effector in interference CRISPR, without any guide RNAs, paradoxically up-regulates key cardiac ion channel genes in human-induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs), responsible for healthy resting membrane potential, repolarization of the action potential, and electrical transmission of signals. These were found to yield expected functional enhancements consistent with a more mature iPSC-CM phenotype, with potentially desirable properties.
ISSN:2752-6542
2752-6542
DOI:10.1093/pnasnexus/pgae027