کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2077688 | 1079738 | 2012 | 5 صفحه PDF | دانلود رایگان |
SummaryHuman trisomies can alter cellular phenotypes and produce congenital abnormalities such as Down syndrome (DS). Here we have generated induced pluripotent stem cells (iPSCs) from DS fibroblasts and introduced a TKNEO transgene into one copy of chromosome 21 by gene targeting. When selecting against TKNEO, spontaneous chromosome loss was the most common cause for survival, with a frequency of ∼10−4, while point mutations, epigenetic silencing, and TKNEO deletions occurred at lower frequencies in this unbiased comparison of inactivating mutations. Mitotic recombination events resulting in extended loss of heterozygosity were not observed in DS iPSCs. The derived, disomic cells proliferated faster and produced more endothelia in vivo than their otherwise isogenic trisomic counterparts, but in vitro hematopoietic differentiation was not consistently altered. Our study describes a targeted removal of a human trisomy, which could prove useful in both clinical and research applications.
► Trisomy correction in Down syndrome iPSCs by gene targeting and negative selection
► Chromosome loss more frequent than other types of mutations
► Comparison of isogenic disomic and trisomic cell lines
► Trisomy 21 slows iPSC proliferation and reduces endothelial differentiation
Journal: - Volume 11, Issue 5, 2 November 2012, Pages 615–619