Generation of an iPSC cohort of isogenic iPSC lines (46-XY and 47-XXY) from a non-mosaic Klinefelter Syndrome Patient (47-XXY) (KAUSTi008-A, KAUSTi008-B, KAUSTi008-C, KAUSTi008-D, KAUSTi008-E, KAUSTi008-F, KAUSTi008-G)
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
KAUST Grant NumberBAS 1077-01-01
Permanent link to this recordhttp://hdl.handle.net/10754/666353
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AbstractKlinefelter Syndrome (KS) is the most common X chromosome aneuploidy in males characterized by highly heterogeneous clinical manifestations including a subtle cognitive impairment and multisystemic disorders such as infertility, metabolic syndrome, gynecomastia and cardiovascular diseases. To date dosage-dependent correlation studies of X-linked genes and low- and high-grade KS clinical phenotypes have not been performed. Here we generated multiple isogenic 47-XXY and 46-XY iPSC lines from one 47-XXY patient. Leveraging on a fully matched genetic background, our cohort represents a highly informative tool to study the impact of X chromosome dosage on KS pathophysiology.
CitationFiacco, E., Alowaysi, M., Astro, V., & Adamo, A. (2020). Generation of an iPSC cohort of isogenic iPSC lines (46-XY and 47-XXY) from a non-mosaic Klinefelter Syndrome Patient (47-XXY) (KAUSTi008-A, KAUSTi008-B, KAUSTi008-C, KAUSTi008-D, KAUSTi008-E, KAUSTi008-F, KAUSTi008-G). Stem Cell Research, 102119. doi:10.1016/j.scr.2020.102119
SponsorsThis work was funded by KAUST baseline (Grant number BAS 1077-01-01) to A.A. and King Abdulaziz City for Science and Technology (KACST) (Grant number RGC/3/3628-01) to M.A. and A.A. The following cell line was obtained from NIGMS Human Genetic Cell Repository at the Coriell Institute for Medical Research: GM03102. We also acknowledge WiCell as the original source of the WA16 hESC line.
JournalStem Cell Research
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Establishment of an iPSC cohort from three unrelated 47-XXY Klinefelter Syndrome patients (KAUSTi007-A, KAUSTi007-B, KAUSTi009-A, KAUSTi009-B, KAUSTi010-A, KAUSTi010-B).Alowaysi, Maryam; Fiacco, Elisabetta; Astro, Veronica; Adamo, Antonio (Stem cell research, Elsevier BV, 2020-10-10) [Article]Klinefelter Syndrome (KS) is caused by the presence of a supernumerary X chromosome. Cytogenetic studies revaled that 80-90% of patients carry a 47-XXY karyotype, while 10-20% of cases are represented by mosaic 46-XY/47-XXY and high-grade aneuploidies 48-XXXY and 48-XXYY. The phenotypic traits of KS are highly variable across individuals and include cognitive dysfunction, metabolic dysregulation, osteoporosis, and cardiovascular diseases. Here, we describe the derivation of multiple 47-XXY iPSC lines from three unrelated KS patients to study the impact of supernumerary X chromosome during early development.
Establishment of iPSC lines from a high-grade Klinefelter Syndrome patient (49-XXXXY) and two genetically matched healthy relatives (KAUSTi003-A, KAUSTi004-A, KAUSTi004-B, KAUSTi005-A, KAUSTi005-B, KAUSTi005-C).Alowaysi, Maryam; Fiacco, Elisabetta; Astro, Veronica; Adamo, Antonio (Stem cell research, Elsevier BV, 2020-09-22) [Article]Klinefelter Syndrome (KS) is the most frequent X chromosome aneuploidy in males. KS patients with 47-XXY, 48-XXXY and 49-XXXXY karyotypes endure inter-individual phenotypic variabilities including infertility, cardiac diseases, metabolic and psychiatric disorders. We derived iPSC lines from a high-grade 49-XXXXY KS and two healthy donors' fibroblasts. Importantly, the healthy controls XY and XX are direct relatives to KS patients, thus enabling functional comparisons of healthy and disease iPSCs with partially matched genetic backgrounds. These iPSC lines provide an unprecedented cellular tool to study KS pathophysiology at the pluripotent stage as well as during differentiation into disease relevant cell types.
Generation of two iPSC lines (KAUSTi001-A, KAUSTi002-A) from a rare high-grade Klinefelter Syndrome patient (49-XXXXY) carrying a balanced translocation t(4,11) (q35,q23).Alowaysi, Maryam; Fiacco, Elisabetta; Astro, Veronica; Adamo, Antonio (Stem cell research, Elsevier BV, 2020-11-30) [Article]Klinefelter Syndrome (KS) is the most common aneuploidy in humans (prevalence: 85-250 per 100,000 born males) and is characterized by one or more supernumerary X-chromosomes (47-XXY, 48-XXXY and 49-XXXXY karyotypes). KS is a multisystemic disorder associated to multiple phenotypic features including cardiac abnormalities, infertility, mental retardation, diabetes and increased cancer risk. Using a non-integrative mRNAs reprogramming approach, we generated two iPSC lines 48-XXXY and 49-XXXXY from a non-mosaic 49-XXXXY KS patient carrying a balanced translocation t(4,11) (q35,q23). These iPSC lines provide a unique cellular platform to study the molecular mechanisms underlying KS pathophysiology.