TY  - JOUR
A1  - Stengel, Felix
A1  - Vulinovic, Franca
A1  - Meier, Britta
A1  - Grütz, Karen
A1  - Klein, Christine
A1  - Capetian, Philipp
T1  - Impaired differentiation of human induced neural stem cells by TOR1A overexpression
JF  - Molecular Biology Reports
N2  - 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.
KW  - dystonia
KW  - DYT1
KW  - torsinA
KW  - TOR1A
KW  - neuronal stem cells
KW  - neuronal differentiation
KW  - inducible expression
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241177
UR  - https://doi.org/10.1007/s11033-020-05390-x
VL  - 47
ER  -