PubMed_ArguminSci  

PubMed:22798143 JSONTXT 49 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 121-269 DRI_Approach denotes The genetic mutation in Friedreich ataxia (FRDA) is a hyperexpansion of the triplet-repeat sequence GAA·TTC within the first intron of the FXN gene.
T2 270-318 DRI_Background denotes Although yeast and reporter construct models for
T3 342-588 DRI_Background denotes expansion have been reported, studies on FRDA pathogenesis and therapeutic development are limited by the availability of an appropriate cell model in which to study the mechanism of instability of the GAA·TTC triplet repeats in the human genome.
T4 589-764 DRI_Background denotes Herein, induced pluripotent stem cells (iPSCs) were generated from FRDA patient fibroblasts after transduction with the four transcription factors Oct4, Sox2, Klf4, and c-Myc.
T5 765-890 DRI_Background denotes These cells were differentiated into neurospheres and neuronal precursors in vitro, providing a valuable cell model for FRDA.
T6 891-1016 DRI_Approach denotes During propagation of the iPSCs, GAA·TTC triplet repeats expanded at a rate of about two GAA·TTC triplet repeats/replication.
T7 1017-1106 DRI_Approach denotes However, GAA·TTC triplet repeats were stable in FRDA fibroblasts and neuronal stem cells.
T8 1107-1348 DRI_Background denotes The mismatch repair enzymes MSH2, MSH3, and MSH6, implicated in repeat instability in other triplet-repeat diseases, were highly expressed in pluripotent stem cells compared with fibroblasts and neuronal stem cells and occupied FXN intron 1.
T9 1349-1402 DRI_Background denotes In addition, shRNA silencing of MSH2 and MSH6 impeded
T10 1426-1436 DRI_Background denotes expansion.
T11 1437-1485 DRI_Approach denotes A specific pyrrole-imidazole polyamide targeting
T12 1509-1599 DRI_Approach denotes DNA partially blocked repeat expansion by displacing MSH2 from FXN intron 1 in FRDA iPSCs.
T13 1600-1635 DRI_Challenge denotes These studies suggest that in FRDA,
T14 1659-1751 DRI_Challenge denotes instability occurs in embryonic cells and involves the highly active mismatch repair system.