ArticleGenome medicine2016
Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model.
Article in Genome medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Inferring translational efficiency from transcriptomes improves noncanonical neoantigen prioritization and cancer patient stratification.NPJ precision oncology · 2026Article
- Tuberous sclerosis complex.Nature reviews. Disease primers · 2026Review
- Neuronal hyperactivity becomes mTORC1 independent due to transcriptional changes in tuberous sclerosis complex disease models.Cell reports · 2025Article
- Genome-Wide Translatome Analysis Following Low-Dose Ketamine to Reveal Novel Targets for Antidepressant Treatment.Synapse (New York, N.Y.) · 2025Article
- The transcriptomic signature of DEPDC5 KO induced mTOR hyperactivation in human neurons and its response to rapamycin treatment.Epilepsia · 2025Article
- Orchestrating Neural Development Through mRNA Translation Regulation.Journal of neurochemistry · 2025Review
- Reply to: Identification of old coding regions disproves the hominoid de novo status of genes.Nature ecology & evolution · 2024Article
- Non-invasive label-free imaging analysis pipeline for in situ characterization of 3D brain organoids.Scientific reports · 2024Article
- Non-Invasive Label-free Analysis Pipeline for In Situ Characterization of Differentiation in 3D Brain Organoid Models.Research square · 2024Article
- Translatome analysis of tuberous sclerosis complex 1 patient-derived neural progenitor cells reveals rapamycin-dependent and independent alterations.Molecular autism · 2023Article
- A twin UGUA motif directs the balance between gene isoforms through CFIm and the mTORC1 signaling pathway.eLife · 2023Article
- Identification of ligand-receptor pairs that drive human astrocyte development.Nature neuroscience · 2023Article
- Genome-wide translation control analysis of developing human neurons.Molecular brain · 2022Article
- NMD is required for timely cell fate transitions by fine-tuning gene expression and regulating translation.Genes & development · 2022Article
- Review
- Angelman Syndrome and Angelman-like Syndromes Share the Same Calcium-Related Gene Signatures.International journal of molecular sciences · 2021Article
- 16p11.2 deletion is associated with hyperactivation of human iPSC-derived dopaminergic neuron networks and is rescued by RHOA inhibition in vitro.Nature communications · 2021Article
- RHOA signaling defects result in impaired axon guidance in iPSC-derived neurons from patients with tuberous sclerosis complex.Nature communications · 2021Article
- Detection of endophenotypes associated with neuropsychiatric deficiencies in a mouse model of tuberous sclerosis complex using diffusion tensor imaging.Brain pathology (Zurich, Switzerland) · 2021Article
- Conserved UBE3A subcellular distribution between human and mice is facilitated by non-homologous isoforms.Human molecular genetics · 2020Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundTuberous sclerosis complex (TSC) is a genetic disease characterized by benign tumor growths in multiple organs and neurological symptoms induced by mTOR hyperfunction. 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 and suggest new targets for treatment.
methodsWe investigate the disease phenotype of TSC by neural differentiation of a human stem cell model that had been deleted for TSC2 by genome editing. Comprehensive genomic analysis was performed by RNA sequencing and ribosome profiling to obtain a detailed genome-wide description of alterations on both the transcriptional and translational level. The molecular effect of mTOR inhibitors used in the clinic was monitored and comparison to published data from patient biopsies and mouse models highlights key pathogenic processes.
resultsTSC2-deficient neural stem cells showed severely reduced neuronal maturation and characteristics of astrogliosis instead. Transcriptome analysis indicated an active inflammatory response and increased metabolic activity, whereas at the level of translation ribosomal transcripts showed a 5'UTR motif-mediated increase in ribosome occupancy. Further, we observed enhanced protein synthesis rates of angiogenic growth factors. Treatment with mTOR inhibitors corrected translational alterations but transcriptional dysfunction persisted.
conclusionsOur results extend the understanding of the molecular pathophysiology of TSC brain lesions, and suggest phenotype-tailored pharmacological treatment strategies.
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