Single-cell sequencing of the human midbrain reveals glial activation and a neuronal state specific to Parkinson’s disease
| العنوان: | Single-cell sequencing of the human midbrain reveals glial activation and a neuronal state specific to Parkinson’s disease |
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| المؤلفون: | Christopher Morris, Bernd Timmermann, Jens Christian Schwamborn, J. Henck, C. Dietrich, Paul Antony, S. Balachandran, Malte Spielmann, Cesar Augusto Prada-Medina, Z. Landoulsi, S. Pachchek, Anne Grünewald, Sascha Sauer, Patrick May, Semra Smajic, Javier Jarazo |
| المصدر: | medRxiv (The Preprint Server for health sciences.) medRxiv |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Parkinson's disease, Microglia, Cell growth, Dopaminergic, Cell cycle, Biology, Biochemistry, biophysics & molecular biology [F05] [Life sciences], medicine.disease, Transcriptome, medicine.anatomical_structure, nervous system, medicine, Unfolded protein response, CADPS2, Biochimie, biophysique & biologie moléculaire [F05] [Sciences du vivant], Neuroscience |
| الوصف: | Parkinson’s disease (PD) etiology is associated with genetic and environmental factors that lead to a loss of dopaminergic neurons. However, the functional interpretation of PD-associated risk variants and how other midbrain cells contribute to this neurodegenerative process are poorly understood. Here, we profiled >41,000 single-nuclei transcriptomes of postmortem midbrain tissue from 6 idiopathic PD (IPD) patients and 5 matched controls. We show that PD-risk variants are associated with glia- and neuron-specific gene expression patterns. Furthermore, Microglia and astrocytes presented IPD-specific cell proliferation and dysregulation of genes related to unfolded protein response and cytokine signalling. IPD-microglia revealed a specific pro-inflammatory trajectory. Finally, we discovered a neuronal cell cluster exclusively present in IPD midbrains characterized by CADPS2 overexpression and a high proportion of cycling cells. We conclude that elevated CADPS2 expression is specific to dysfunctional dopaminergic neurons, which have lost their dopaminergic identity and unsuccessful attempt to re-enter the cell cycle. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::978c2e8a1978a622f58cf6fa9cce61f4 http://orbilu.uni.lu/handle/10993/49376 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....978c2e8a1978a622f58cf6fa9cce61f4 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |