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E-GEOD-78959 - Modeling the Neuropathology of Tuberous Sclerosis with Human Stem Cells Reveals a Role for Inflammation and Angiogenic Growth Factors [Cell Model]

Released on 25 July 2016, last updated on 30 July 2016
Homo sapiens
Samples (24)
Protocols (3)
Tuberous sclerosis complex (TSC) is a rare genetic disease characterized by mTOR hyperfunction induced benign tumor growths in multiple organs and neurological symptoms. Because the molecular pathology is highly complex and the etiology poorly understood we employed a defined human neuronal model with a single mTOR activating mutation to dissect the disease-relevant molecular responses driving the neuropathology. TSC2 deficient neural stem cells showed severely reduced neuronal functional maturation and characteristics of astrogliosis instead. Accordingly, transcriptome analysis uncovered an inflammatory response and increased metabolic activity, while ribosome profiling revealed excessive translation of ribosomal transcripts and higher synthesis rates of angiogenic growth factors. Treatment with mTOR inhibitors corrected translational alterations but not transcriptional dysfunction. These results extend our understanding of the molecular pathophysiology of TSC brain lesions, and suggest phenotype-tailored pharmacological treatment strategies. Two TSC+/- cell lines and two TSC-/- cell lines were independently generated from wild-type human embryonic stem cells by genome editting with zinc finger nucleases. Two cell lines were handled in the same way but without any known human gene editted and they are used as negative controls. Two independent biological replicates of each of the six cell lines are profiled with ribosome profiling technique.
Experiment type
RNA-seq of coding RNA 
Jitao David Zhang <>, Anna Kiialainen, Felix C Weber, Gene W Yeo, Jitao D Zhang, Martin Ebeling, Michel Theron, Nadine Ruderisch, Nikolaos Berntenis, Nils Grabole, Olivia Spleiss, Ravi Jagasia, Stefan Aigner, Veronica Costa
Exp. designProtocolsVariablesProcessedSeq. reads
Investigation descriptionE-GEOD-78959.idf.txt
Sample and data relationshipE-GEOD-78959.sdrf.txt
Additional data (1)