Impaired differentiation of human induced neural stem cells by TOR1A overexpression.

Impaired differentiation of human induced neural stem cells by TOR1A overexpression. Mol Biol Rep. 2020 Apr 01;: Authors: Stengel F, Vulinovic F, Meier B, Grütz K, Klein C, Capetian P Abstract DYT-TOR1A is the most common inherited dystonia caused by a three nucleotide (GAG) deletion (dE) in the TOR1A gene. Death early after birth and cortical anomalies of the full knockout in rodents underscore its developmental importance. We therefore explored the timed effects of TOR1A-wt and TOR1A-dE during differentiation in a human neural in vitro model. We used lentiviral tet-ON expression of TOR1A-wt and -dE in induced neural stem cells derived from healthy donors. Overexpression was induced during proliferation of neural precursors, during differentiation and after differentiation into mature neurons. Overexpression of both wildtype and mutated protein had no effect on the viability and cell number of neural precursors as well as mature neurons when initiated before or after differentiation. However, if induced during differentiation, overexpression of TOR1A-wt and -dE led to a pronounced reduction of mature neurons in a dose dependent manner. Our data underscores the importance of physiological expression levels of TOR1A as crucial for proper neuronal differentiation. We did not find evidence for a specific impact of the mutated TOR1A on neuronal maturation. PMID: 32239467 [PubMed - as supplied by publisher]
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research

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SOX2 (OMIM: 184429) encodes for a transcription factor of the SRY (sex-determining region Y)-related high-mobility-group box family which regulates pluripotency of human embryonic stem cells and is indispensable for coordinated embryogenesis. Pathogenic variants within this gene are associated with autosomal dominant syndromic forms of uni- or bilateral micro- or anophthalmia and a wide range of non-ocular features including neurological, gastrointestinal, genital, skeletal, cardiovascular, endocrine and renal anomalies [1].
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Tags: Letter to the Editor Source Type: research
Publication date: Available online 17 January 2019Source: Stem Cell ReportsAuthor(s): Zoe Noakes, Francesca Keefe, Claudia Tamburini, Claire M. Kelly, Maria Cruz Santos, Stephen B. Dunnett, Adam C. Errington, Meng LiSummaryStriatal interneurons are born in the medial and caudal ganglionic eminences (MGE and CGE) and play an important role in human striatal function and dysfunction in Huntington's disease and dystonia. MGE/CGE-like neural progenitors have been generated from human pluripotent stem cells (hPSCs) for studying cortical interneuron development and cell therapy for epilepsy and other neurodevelopmental disorders...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
A Chinese scientist shocked the scientific community a couple of days ago with the announcement of having modified the very blueprint of life. If his claims are true, he tried to bestow two baby girls the ability to resist possible future infections with HIV. The outrage shows that humanity is not prepared to utilize the power of gene editing on embryos yet. We have no idea about the biological consequences, and we haven’t tackled the necessary legal and ethical issues. Genes to become toys of the “Gods”? Humanity has come a long way since Aldous Huxley pinned down how methods of genetic engineering, bio...
Source: The Medical Futurist - Category: Information Technology Authors: Tags: Bioethics Future of Medicine Genomics designer babies designer baby Gene gene editing genes Genome genome sequencing Health Healthcare healthcare system Innovation technology Source Type: blogs
Publication date: Available online 1 October 2018Source: Stem Cell ResearchAuthor(s): Hauke Baumann, Magdalena Jahn, Alexander Muenchau, Michaela Trilck-Winkler, Katja Lohmann, Philip SeiblerAbstractMutations in THAP1 (THAP domain-containing apoptosis-associated protein 1) cause a form of early-onset, isolated dystonia (DYT-THAP1, aka DYT6). Here, we describe the generation of eight human induced pluripotent stem cell (iPSC) lines of manifesting and non-manifesting carriers of the THAP1 mutations p.Lys158Asnfs*23 or p.Arg13His (each 4 lines). Dermal fibroblasts were reprogrammed using non-integrating Sendai virus. The iPSC...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Publication date: September 2018Source: Molecular Genetics and Metabolism Reports, Volume 16Author(s): Kishore R. Kumar, Gautam Wali, Ryan L. Davis, Amali C. Mallawaarachchi, Elizabeth E. Palmer, Velimir Gayevskiy, Andre E. Minoche, David Veivers, Marcel E. Dinger, Alan Mackay-Sim, Mark J. Cowley, Carolyn M. SueAbstractZellweger syndrome spectrum disorders are caused by mutations in any of at least 12 different PEX genes. This includes PEX16, an important regulator of peroxisome biogenesis. Using whole genome sequencing, we detected previously unreported, biallelic variants in PEX16 [NM_004813.2:c.658G>A, p.(Ala220Thr) ...
Source: Molecular Genetics and Metabolism Reports - Category: Genetics & Stem Cells Source Type: research
egner F Abstract X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disorder endemic to Panay Island (Philippines). Patients present with generalizing dystonia and parkinsonism. Genetic changes surrounding the TAF1 (TATA-box binding protein associated factor 1) gene have been associated with XDP inducing a degeneration of striatal spiny projection neurons. There is little knowledge about the pathophysiology of this disorder. Our objective was to generate and analyze an in-vitro model of XDP based on striatal neurons differentiated from induced pluripotent stem cells (iPSC). We generated iPSC from patient ...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
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Source: Cell - Category: Cytology Source Type: research
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Source: Stem Cell Research - Category: Stem Cells Source Type: research
This study demonstrated that increased murine transplant-recipient age (adult vs neonate) resulted in decreased graft survival and volume/rostro-caudal spread after six weeks in vivo, regardless of "age" of the cells transplanted. Importantly, this study implicates that the in vivo setting may provide a better neurogenic niche for iPSC-based modeling as compared to the in vitro setting. Together, these results recapitulate findings from fetal striatal progenitor transplantation studies and further demonstrate the influence of the host environment on cellular survival and maturation. PMID: 28760579 [PubMed - ...
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Source: Stem Cell Reports - Category: Stem Cells Source Type: research
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