Modeling human brain diseases using pluripotent stem cells
Het modelleren van humane hersenziektes met behulp van pluripotente stamcellen
Well into the 21st century, it is the functioning of the organ the brain that remains uncomprehended. Only recently the unravelment of the many cell types the brain houses commenced; together with what their role is, how they emerge and how they develop. Similarly the biological communication systems involved including their miscommunication in diseased state are only slowly starting to be understood.
The neurosciences have always been behind in its advancement compared to other life science specialties. With the emergence of the cellular neuroscience in the late nineteenth century, this backlog had not to do with lack of bright minds. The inaccessibility of living human brain tissue had greatly compromised progress. Nevertheless, with the advent of human induced pluripotent stem cell (hIPS) technology ten years ago, the field rapidly started to change. Human IPS technology allowed the in vitro generation of different cell types of the human brain and a plethora of publications instructed on how to optimally obtain and maintain them. Within four years this technique was applied to study human-specific brain diseases such as Angelman syndrome and schizophrenia. And disease modeling only became easier with the development of CRISPR-Cas9 editing technology. Embraced with these new skills the field of the molecular neurosciences brook free.
This thesis shows a collection of work on the use of hIPS technology and its application for fundamental human biological research as well as human brain disease modeling: it presents a protocol to generate functional in vitro human neural cultures from pluripotent stem cells. Next to that, it shows how this protocol is used to study expression of human BDNF, a neurotrophin involved in many processes of brain development. Lastly, in vitro disease models are presented on Angelman Syndrome (AS), Fragile X-syndrome (FXS) and Parkinson’s Disease (PD).
|S.A. Kushner (Steven) , F.M.S. Vrij (Femke)|
|Erasmus University Rotterdam|
|Organisation||Department of Psychiatry|
Munshi, S.T. (2019, November 6). Modeling human brain diseases using pluripotent stem cells. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/109094
|Shashini-Munshi-Stellingen-1-.pdf , 518kb|
|109094_Chapter_1-General_Introduction.pdf Final Version , 242kb|
|109094_Chapter_2-A_simplified_protocol_for_differentiatio.pdf Final Version , 1mb|
|109094_Chapter_3-Identification_of_novel_activity-depende.pdf Final Version , 649kb|
|109094_Chapter_4-Subcellular_localization_of_mouse_and_hu.pdf Final Version , 751kb|
|109094_Chapter_5-Epigenetic_Characterization_of_the_FMR1.pdf Final Version , 1mb|
|109094_Chapter_6-A_functional_variant_in_the_miR-142_prom.pdf Final Version , 1mb|
|109094_Chapter_7-General_discussion.pdf Final Version , 196kb|