Demonstration of genetic manipulations for in vitro modeling
November 2013
University of Konstanz, Konstanz, Germany
The lack of differentiated human cell types and the difficulties associated with their use and manipulation have previously hindered the development of human-based in vitro models. Here, a human conditionally-immortalized mesencephalic cell line is used to apply genetic modifications in the proliferative state to study their effects in the post-mitotic neurons. Several genetic modifications are done in this study, and the results show that it is possible to induce overexpression or knockdown of Parkinson's related proteins to modulate the physiological outcome of the cells. Also, the researchers introduce reporter genes to track the dynamics of different proteins or organelles in different cell compartments, which allows studying the modifications induced by toxic compounds used in Parkinson's models. Overall, a strategy is presented that offers the possibility to genetically manipulate a human neural progenitor cell line that can be differentiated into dopaminergic neurons to study changes in protein and organelle physiology in different pathological conditions in post-mitotic human cells.
Generation of genetically-modified human differentiated cells for toxicological tests and the study of neurodegenerative diseases
Stefan Schildknecht
Added on: 09-02-2021
[1] https://www.altex.org/index.php/altex/article/view/363[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
