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Single-cell sequencing of the human midbrain reveals glial activation and a neuronal state specific to Parkinson’s disease
Smajic, Semra; Prada-Medina, Cesar A.; Landoulsi, Zied et al.
2020
 

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Abstract :
[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Smajic, Semra ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Molecular and Functional Neurobiology
Prada-Medina, Cesar A.
Landoulsi, Zied ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Dietrich, Carola
Jarazo, Javier ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Henck, Jana
Balachan, Saranya
Pachchek, Sinthuja  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Morris, Christopher M.
Antony, Paul ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Timmermann, Bernd
Sauer, Sascha
Schwamborn, Jens Christian ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Developmental and Cellular Biology
May, Patrick  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Grünewald, Anne  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Molecular and Functional Neurobiology
Spielmann, Malte
More authors (6 more) Less
Language :
English
Title :
Single-cell sequencing of the human midbrain reveals glial activation and a neuronal state specific to Parkinson’s disease
Publication date :
2020
FnR Project :
FNR9631103 - Modelling Idiopathic Parkinson'S Disease-associated Somatic Variation In Dopaminergic Neurons, 2015 (01/01/2016-31/12/2022) - Anne Grünewald
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