We developed 24 new human induced pluripotent stem cell (hiPSC) lines from postmortem donors with a range of sporadic Alzheimer’s disease (AD) neuropathology and comorbid aging-related neurodegenerative disorders from prospective cohort studies in Seattle, WA. Leptomeningeal tissue was collected at the time of brain removal and primary fibroblast cultures derived as the parent cell source for reprogramming. Extensive clinical, genetic, and neuropathologic data are available for each brain donor, including genotyping for polygenic Alzheimer’s disease risk through the endolysosomal pathway. These hiPSC lines will advance our understanding of the cellular mechanisms involved in AD pathogenesis, particularly the underlying genetic contributions to the disease, and serve as a screening tool for drug development.
Spinocerebellar Ataxia 27B (SCA27B) is a late-onset neurodegenerative disorder caused by a heterozygous pathogenic GAA•TTC repeat expansion in intron 1 of FGF14. Despite being a common genetic cause of adult-onset cerebellar ataxia, the underlying molecular mechanisms remain unclear. Here, we performed simultaneous reprogramming and CRISPR-Cas9 genome editing to generate four induced pluripotent stem cell (iPSC) lines and their respective isogenic gene-corrected controls. All lines exhibited normal karyotypes, pluripotency, and trilineage differentiation capacity. These paired iPSC lines provide a valuable platform for investigating the pathomechanism(s) of SCA27B and can be used for screening of potential therapeutic treatments.
Cyclin-dependent kinase inhibitor 2A ( CDKN2A /p16 INK4a ) is a senescence-associated cell-cycle regulator that inhibits CDK4/6-dependent RB phosphorylation and cell-cycle progression. Here, we established a doxycycline-inducible p16 INK4a knock-in human embryonic stem cell line by targeting a Tet-On expression cassette into the AAVS1 safe-harbor locus. The generated line retained pluripotency marker expression, tri-lineage differentiation potential, and a normal karyotype. Doxycycline treatment induced dose-dependent increases in p16 INK4a expression and ZsGreen reporter expression. This cell line provides a foundational resource for developing p16 INK4a -associated cellular senescence models across multiple stem cell-derived lineages.
CRISPR/Cas9 was used to introduce two different FTSJ1 frameshift mutations into an existing human male iPSC line (UMGWi004-B). No additional genomic or chromosomal changes were detected. The modified iPSC express different stem cell markers and can be induced to differentiate into cells from all three germ layers. FTSJ1 is ubiquitously expressed and mutations in this X-chromosomal gene are involved in an intellectual developmental disorder (OMIM: #309549). These cells can be used to model the disease at the cellular and organoid level in their original state or after differentiation into cell types of interest.
Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome characterized by defective erythropoiesis and increased risk of congenital malformations and cancer. Progress in understanding DBA pathophysiology has been hindered by the lack of physiologically relevant disease models, limited public funding, and low commercial interest. Here, we generated four induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) obtained from members of a family carrying a heterozygous c.184C > T RPS19 mutation (p.Arg62Trp) exhibiting variable clinical manifestations of DBA. This well-characterized iPSC resource facilitates disease modelling and therapeutic development and is available to both academic and commercial researchers.
