English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Single-cell sequencing of the human midbrain reveals glial activation and a neuronal state specific to Parkinson's disease

Smajic, S., Prada-Medina, C. A., Landoulsi, Z., Dietrich, C., Jarazo, J., Henck, J., et al. (2020). Single-cell sequencing of the human midbrain reveals glial activation and a neuronal state specific to Parkinson's disease. medRxiv (The Preprint Server for health sciences.). doi:10.1101/2020.09.28.20202812.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files
hide Files
:
Smajić_2020.pdf (Preprint), 3MB
Name:
Smajić_2020.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2020, The author(s)

Locators

show

Creators

show
hide
 Creators:
Smajic, Semra , Author
Prada-Medina, Cesar Augusto , Author
Landoulsi, Zied , Author
Dietrich, Carola1, Author              
Jarazo, Javier , Author
Henck, Jana1, Author              
Balachandran, Saranya , Author
Pachchek, Sinthuja, Author
Morris, Christopher M., Author
Anthony, Paul, Author
Timmermann, Bernd2, Author              
Sauer, Sascha, Author
Schwamborn, Jens C. , Author
May, Patrick, Author
Grunewald, Anne , Author
Spielmann, Malte1, Author              
Affiliations:
1Human Molecular Genomics (Malte Spielmann), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3014183              
2Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

Content

show
hide
Free keywords: -
 Abstract: 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.

Details

show
hide
Language(s): eng - English
 Dates: 2020-09-30
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1101/2020.09.28.20202812
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: medRxiv (The Preprint Server for health sciences.)
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: -