Reference : Single-cell sequencing of the human midbrain reveals glial activation and a neuronal ...
E-prints/Working papers : Already available on another site
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/49376
Single-cell sequencing of the human midbrain reveals glial activation and a neuronal state specific to Parkinson’s disease
English
Smajic, Semra mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Molecular and Functional Neurobiology >]
Prada-Medina, Cesar A. []
Landoulsi, Zied mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core >]
Dietrich, Carola []
Jarazo, Javier mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Henck, Jana []
Balachan, Saranya []
Pachchek, Sinthuja mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience >]
Morris, Christopher M. []
Antony, Paul mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience >]
Timmermann, Bernd []
Sauer, Sascha []
Schwamborn, Jens Christian mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Developmental and Cellular Biology >]
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core >]
Grünewald, Anne mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Molecular and Functional Neurobiology >]
Spielmann, Malte []
2020
No
[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.
Researchers
http://hdl.handle.net/10993/49376
https://www.medrxiv.org/content/10.1101/2020.09.28.20202812v1.full.pdf
FnR ; FNR9631103 > Anne Grünewald > Model IPD > Modelling Idiopathic Parkinson’S Disease-associated Somatic Variation In Dopaminergic Neurons > 01/01/2016 > 31/12/2022 > 2015

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
2020.09.28.20202812v1.full.pdfAuthor preprint2.7 MBView/Open

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.