| dc.contributor.advisor | Mansouri, Ahmed Prof. Dr. | |
| dc.contributor.author | Liao, Mei-Chih | |
| dc.date.accessioned | 2014-06-02T09:10:07Z | |
| dc.date.available | 2014-06-02T09:10:07Z | |
| dc.date.issued | 2014-06-02 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0022-5ED2-6 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-4529 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Patient-Specific Induced Pluripotent Stem Cell Models of Parkinson’s Disease | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Wimmer, Ernst A. Prof. Dr. | |
| dc.date.examination | 2013-10-21 | |
| dc.description.abstracteng | Parkinson’s disease (PD) is one of the common neurodegenerative diseases. In particular, it affects the elderly and associates with the movement disorder. The hallmarks of PD are progressive loss of midbrain dopaminergic neurons and the appearance of Lewy bodies in the affected neurons. At present, the etiology of PD is not well understood and may reflect the interactions of environmental and genetic factors. The main hurdle in studying PD pathogenesis is the inaccessibility to the brain tissues from PD patients. Recent advances in cellular reprogramming now allow an alternative approach for investigating PD. PD patients’ dermal fibroblasts can be converted to the pluripotent state, and further differentiated to the disease relevant cell type, dopaminergic neurons. Such PD affected neurons in culture represent a promising departure point for exploring the pathogenic factors of PD.
Here, we have generated disease specific human induced pluripotent stem cells (hiPSCs) from 3 individual idiopathic PD patients and 2 healthy persons’ fibroblast. We applied a single lentiviral vector (hSTEMCCA-loxP) encoding OCT4, KLF4, SOX2, and c-MYC, and subsequently were able to generate the transgene-free hiPSCs using Cre-loxP recombination. The genomic constitutions of PD-hiPSCs were found identical to their parental fibroblasts by DNA fingerprinting. The characteristics of PD-hiPSCs resembled human embryonic stem cells (hESCs) displaying the expression of pluripotency marker genes, and the capability of differentiating into the three germ layers. Neural precursors were derived from PD-hiPSCs, and then examined by transcriptome analysis. Our results revealed some differentially expressed genes involved in axon guidance and neuron differentiation. Among those candidates, FGF20 was down regulated in PD patients. By Directed differentiation of floor-plate (FP) derived midbrain dopaminergic (mDA) neurons from hiPSCs, large population of specific midbrain dopaminergic neurons could be achieved. We exposed these control and PD specific hiPSCs derived mDA neurons to mitochondrial stress. PD-hiPSC derived mDA neurons were susceptible to CCCP treatments. Interestingly, FGF20 was able to counteract these cellular stresses. FGF20, therefore, might hold the capacity for dopaminergic neuroprotection. | de |
| dc.contributor.coReferee | Wodarz, Andreas Prof. Dr. | |
| dc.contributor.thirdReferee | Paulus, Walter Prof. Dr. | |
| dc.contributor.thirdReferee | Schuh, Reinhard Prof. Dr. | |
| dc.contributor.thirdReferee | Dosch, Roland Dr. | |
| dc.subject.eng | Parkinson's Disease | de |
| dc.subject.eng | Induced pluripotent stem cell | de |
| dc.subject.eng | Dopaminergic Neuron | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0022-5ED2-6-1 | |
| dc.affiliation.institute | Biologische Fakultät für Biologie und Psychologie | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 786838256 | |