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Coding and small non-coding transcriptional landscape of tuberous sclerosis complex cortical tubers: implications for pathophysiology and treatment
JD. Mills, AM. Iyer, J. van Scheppingen, A. Bongaarts, JJ. Anink, B. Janssen, TS. Zimmer, WG. Spliet, PC. van Rijen, FE. Jansen, M. Feucht, JA. Hainfellner, P. Krsek, J. Zamecnik, K. Kotulska, S. Jozwiak, A. Jansen, L. Lagae, P. Curatolo, DJ....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
NLK
Directory of Open Access Journals
od 2011
Free Medical Journals
od 2011
Nature Open Access
od 2011-12-01
PubMed Central
od 2011
Europe PubMed Central
od 2011
ProQuest Central
od 2011-01-01
Open Access Digital Library
od 2011-01-01
Open Access Digital Library
od 2011-01-01
Health & Medicine (ProQuest)
od 2011-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2011
Springer Nature OA/Free Journals
od 2011-12-01
- MeSH
- dítě MeSH
- dospělí MeSH
- epilepsie genetika MeSH
- genetická transkripce genetika MeSH
- hamartin genetika MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mozková kůra fyziologie MeSH
- mTORC1 genetika MeSH
- mutace genetika MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neurony fyziologie MeSH
- předškolní dítě MeSH
- signální transdukce genetika MeSH
- tuberin genetika MeSH
- tuberózní skleróza genetika MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- myši MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1). TSC is associated with autism, intellectual disability and severe epilepsy. Cortical tubers are believed to represent the neuropathological substrates of these disabling manifestations in TSC. In the presented study we used high-throughput RNA sequencing in combination with systems-based computational approaches to investigate the complexity of the TSC molecular network. Overall we detected 438 differentially expressed genes and 991 differentially expressed small non-coding RNAs in cortical tubers compared to autopsy control brain tissue. We observed increased expression of genes associated with inflammatory, innate and adaptive immune responses. In contrast, we observed a down-regulation of genes associated with neurogenesis and glutamate receptor signaling. MicroRNAs represented the largest class of over-expressed small non-coding RNA species in tubers. In particular, our analysis revealed that the miR-34 family (including miR-34a, miR-34b and miR-34c) was significantly over-expressed. Functional studies demonstrated the ability of miR-34b to modulate neurite outgrowth in mouse primary hippocampal neuronal cultures. This study provides new insights into the TSC transcriptomic network along with the identification of potential new treatment targets.
Department of Heemstede The Netherlands
Department of Medicine Brigham and Women's Hospital Boston Massachusetts USA
Department of Neurology University of Maryland School of Medicine Baltimore MD USA
Department of Pathology Academic Medical Center University of Amsterdam Amsterdam The Netherlands
Department of Pathology University Medical Center Utrecht Utrecht The Netherlands
Department of Pediatrics Medical University Vienna Vienna Austria
GenomeScan BV Leiden The Netherlands
Institute of Neurology Medical University Vienna Vienna Austria
Citace poskytuje Crossref.org
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