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SRP122898
Homo sapiens
16 Downloadable Samples
Illumina HiSeq 2000
Description
Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of b-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells with CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB-corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids but not the HEXB-corrected organoids accumulated GM2 ganglioside, and exhibited increased size and cellular proliferation compared with the HEXB-corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses Overall design: Sandhoff disease and corrected cerebral organoids grown for 8 and 10 weeks were analyzed: four samples at each time point, each consisting of 4–6 pooled organoids, for both Sandhoff and corrected. Whole transcriptome from Sandhoff disease and corrected organoids for both time points were generated by deep sequencing on an Illumina HiSeq 2500.
Publication Title
Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The aim of this study was to compare the roles of the E6 proteins from HPV18 and HPV11, a high-risk and low-risk type, and to evaluate the effect of these two types of E6 proteins on gene expression
Publication Title
Delineation of the HPV11E6 and HPV18E6 Pathways in Initiating Cellular Transformation.
Sample Metadata Fields
Treatment
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