Paradoxical effects of ZIM3, a CRISPRi effector, on human induced pluripotent stem-cell-derived cardiomyocyte electrophysiology.
Julie L HanYuli W HeinsonMaria R PozoWeizhen LiEmilia EntchevaPublished in: PNAS nexus (2024)
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.
Keyphrases
- high glucose
- endothelial cells
- induced pluripotent stem cells
- diabetic rats
- genome wide
- regulatory t cells
- dendritic cells
- pluripotent stem cells
- crispr cas
- drug induced
- heart failure
- heart rate
- oxidative stress
- blood pressure
- dna methylation
- immune response
- mass spectrometry
- type iii
- risk assessment
- human health
- genome editing
- solid phase extraction
- tandem mass spectrometry