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+---
+layout: default
+order: -1
+title: "Cell cycle arrest of neural progenitors causes impaired dopaminergic neuronal differentiation in GBA associated Parkinson’s disease midbrain organoids"
+permalink: /frozen/xfh3-a153
+---
+
+{% rtitle Cell cycle arrest of neural progenitors causes impaired dopaminergic neuronal differentiation in GBA associated Parkinson’s disease midbrain organoids %}
+Isabel Rosety, Alise Zagare, Claudia Saraiva, Sarah Nickels, Paul Antony, Catarina Almeida, Enrico Glaab, Rashi Halder, Javier Jarazo, Thomas Rauen, Hans R. Schöler, Silvia Bolognin, Thomas Sauter, Rejko Krüger, Jens Schwamborn
+{% endrtitle %}
+
+{% rblock Abstract %}
+The mechanisms underlying Parkinson's disease (PD) etiology are only partially understood despite intensive research conducted in the field. Recent evidence suggests that early neurodevelopmental defects might play a role in cellular susceptibility to neurodegeneration. To study the early developmental contribution of GBA mutations in PD we used patient-derived iPSCs carrying a heterozygous N370S mutation in the GBA gene. Patient-specific midbrain organoids displayed GBA-PD relevant phenotypes such as reduction of GCase activity, autophagy impairment and mitochondrial dysfunction. Genome-scale metabolic (GEM) modeling predicted changes in lipid metabolism which were validated with lipidomics analysis, showing significant differences in the lipidome of GBA-PD. In addition, patient-specific midbrain organoids exhibited an increase in the neural progenitor population showing signs of cellular senescence. This was accompanied by a decrease in the number and complexity of dopaminergic neurons. These results provide insights into how GBA mutations may lead to neurodevelopmental defects thereby predisposing to PD pathology.
+{% endrblock %}
+
+{% rblock Data %}
+The complete Dataset is available [here](https://webdav-r3lab.uni.lu/public/data/xfh3-a153/). It is subdivided into originals (raw data) and partials (analysis) specific to each figure and supplementary figure present in the manuscript. 
+{% endrblock %}
+
+{% rblock source code %}
+The scripts used to analyse the data are available [here](https://gitlab.lcsb.uni.lu/dvb/rosety_2022). 
+{% endrblock %}
+
+{% endrgridblock %}