GSE125838 Silencing Trisomy 21 with XIST in Neural Stem Cells Promotes Neuronal Differentiation (single cells)

Contributors : Jan T Czerminski ; Jeanne B LawrenceSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAlthough Down Syndrome (DS) is the leading genetic cause of intellectual disability in children, the developmental pathogenesis remains largely unknown, and better strategies are needed to investigate this. We previously showed that one copy of chromosome 21 can be epigenetically silenced in DS iPSCs by insertion of an XIST transgene, which produces a non-coding RNA that normally silences one X chromosome in female cells. XIST was shown to induce heterochromatin and silence transcription across chromosome 21 in pluripotent stem cells, the natural developmental context of XIST function. Prior literature indicated that initiation of chromosome silencing is only possible within 48 hours of mES cell differentiation, however it would be highly advantageous experimentally if trisomy silencing could be initiated in differentiated cells, and this is critical for any therapeutic potential of XIST. Here we use RNAseq and molecular cytology to investigate the effectiveness of XIST for trisomy silencing in cells undergoing in vitro neural differentiation and examine the potential cell phenotypic effects of chromosomal silencing. Induction of XIST from the onset of differentiation resulted in comprehensive silencing of chromosome 21 genes, providing a powerful approach to examine effects of trisomy on neurogenesis. To determine whether human neural stem...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research