E-GEOD-52249 - Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21 [RNA-seq]

Released on 1 December 2013, last updated on 3 June 2014
Homo sapiens
Samples (7)
Protocols (1)
Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD-SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) on chromosome 21 likely contribute to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects. mRNA-seq profiling of iPS cells (4 euploid and 3 trisomy 21) derived from fibroblasts of monozygotic twins discordant for trisomy 21
Experiment type
RNA-seq of coding RNA 
Audrey Letourneau <audrey.letourneau@unige.ch>, Anis Feki, Federico A Santoni, Frédérique Béna, Iwona Grad, M.Reza Sailani, Marie F Pelte, Michel Guipponi, Sophie Dahoun, Stefania Gimelli, Stylianos E Antonarakis, Youssef Hibaoui
Exp. designProtocolsVariablesProcessedSeq. reads
Investigation descriptionE-GEOD-52249.idf.txt
Sample and data relationshipE-GEOD-52249.sdrf.txt