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Turan, N.

Publications and source records attributed to Turan, N..

3 recordsLinked to original sources

A new NHGRI Sample Repository for Human Genetic Research collection of induced pluripotent stem cell lines.

We describe here a new NHGRI Sample Repository for Human Genetic Research collection of induced pluripotent stem cell (iPSC) lines reprogrammed from whole blood derived peripheral blood mononuclear cells (PBMCs). PBMCs were reprogrammed using Sendai viral vectors carrying transcription factors OCT4, SOX2, KLF4, and c-MYC. All iPSC lines exhibit a normal karyotype, express common stemness and pluripotency markers, and demonstrate the ability to differentiate into cell types representing all three germ layers. This iPSC collection (n=7) will have accompanying public, near telomere to telomere genomic data through the Human Pangenome Reference Consortium, and provides an invaluable new in vitro resource for studying common genetic and genomic variation and its functional implications.

cell biology↗

New iPSC resource with long-read whole genome sequencing characterizations for enhanced in vitro modeling

Here we present a new iPSC resource of apparently healthy subject biospecimens available to the research community through the National Institute of General Medical Sciences Human Genetic Cell Repository (NIGMS Repository). This resource includes five iPSCs and matched parental cell lines with accompanying publicly available, HiFi whole-genome sequencing data. Structural variant (SV) and single nucleotide variant (SNV) concordance between iPSC and parental lines was generally high; however, we found a notable reduction in concordance between the iPSC reprogrammed with retroviral reprogramming and its parental line consistent with previous work showing newer Sendai approaches to be more robust in preserving genomic integrity. This iPSC resource additionally includes pharmacogenomic and human leukocyte antigen (HLA) gene annotations as well as a set of user-friendly, web-based search tools to visualize and explore SVs and SNVs. This new resource is designed to offer a highly characterized set of in vitro models for research into cell-type specific functional characterization of genetic, genomic and pharmacogenomic variation. More generally, these renewable biospecimens and genomic data search tools are available to the scientific community to support high-quality and reproducible biomedical research.

genomics↗

Myofibroblast Senescence Promotes Arrhythmogenic Remodeling in the Aged Infarcted Rabbit Heart

Progressive tissue remodeling after myocardial infarction (MI) promotes cardiac arrhythmias. This process is well studied in young animals, but little is known about pro-arrhythmic changes in aged animals. Senescent cells accumulate with age and accelerate age-associated diseases. Senescent cells interfere with cardiac function and outcome post-MI with age, but studies have not been performed in large animals, and the mechanisms are unknown. Here, we investigated the role of senescence in regulating inflammation, fibrosis, and arrhythmogenesis in young and aged infarcted rabbits. Aged rabbits exhibited increased peri-procedural mortality and arrhythmogenic electrophysiological remodeling at the infarct border zone (IBZ) compared to young rabbits. Studies of the aged infarct zone revealed persistent myofibroblast senescence and increased inflammatory signaling over a twelve-week timecourse. Senescent IBZ myofibroblasts in aged rabbits appear to be coupled to myocytes, and our computational modeling showed that senescent myofibroblast- cardiomyocyte coupling prolongs action potential duration (APD) and facilitates conduction block permissive of arrhythmias. Aged infarcted human ventricles show levels of senescence consistent with aged rabbits, and senescent myofibroblasts also couple to IBZ myocytes. Our findings suggest that senolytic drugs may mitigate arrhythmias post-MI.

cell biology↗