Advanced

Single-cell RNA sequencing reveals midbrain dopamine neuron diversity emerging during mouse brain development

Tiklová, Katarína; Björklund, Åsa K.; Lahti, Laura; Fiorenzano, Alessandro LU ; Nolbrant, Sara LU ; Gillberg, Linda; Volakakis, Nikolaos; Yokota, Chika; Hilscher, Markus M. and Hauling, Thomas, et al. (2019) In Nature Communications 10(1).
Abstract

Midbrain dopamine (mDA) neurons constitute a heterogenous group of cells that have been intensely studied, not least because their degeneration causes major symptoms in Parkinson's disease. Understanding the diversity of mDA neurons - previously well characterized anatomically - requires a systematic molecular classification at the genome-wide gene expression level. Here, we use single cell RNA sequencing of isolated mouse neurons expressing the transcription factor Pitx3, a marker for mDA neurons. Analyses include cells isolated during development up until adulthood and the results are validated by histological characterization of newly identified markers. This identifies seven neuron subgroups divided in two major branches of... (More)

Midbrain dopamine (mDA) neurons constitute a heterogenous group of cells that have been intensely studied, not least because their degeneration causes major symptoms in Parkinson's disease. Understanding the diversity of mDA neurons - previously well characterized anatomically - requires a systematic molecular classification at the genome-wide gene expression level. Here, we use single cell RNA sequencing of isolated mouse neurons expressing the transcription factor Pitx3, a marker for mDA neurons. Analyses include cells isolated during development up until adulthood and the results are validated by histological characterization of newly identified markers. This identifies seven neuron subgroups divided in two major branches of developing Pitx3-expressing neurons. Five of them express dopaminergic markers, while two express glutamatergic and GABAergic markers, respectively. Analysis also indicate evolutionary conservation of diversity in humans. This comprehensive molecular characterization will provide a valuable resource for elucidating mDA neuron subgroup development and function in the mammalian brain.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
10
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85061049996
ISSN
2041-1723
DOI
10.1038/s41467-019-08453-1
language
English
LU publication?
yes
id
a3bb49e8-86ba-487b-8efc-d2466ee9c708
date added to LUP
2019-02-11 12:10:39
date last changed
2019-08-14 04:32:22
@article{a3bb49e8-86ba-487b-8efc-d2466ee9c708,
  abstract     = {<p>Midbrain dopamine (mDA) neurons constitute a heterogenous group of cells that have been intensely studied, not least because their degeneration causes major symptoms in Parkinson's disease. Understanding the diversity of mDA neurons - previously well characterized anatomically - requires a systematic molecular classification at the genome-wide gene expression level. Here, we use single cell RNA sequencing of isolated mouse neurons expressing the transcription factor Pitx3, a marker for mDA neurons. Analyses include cells isolated during development up until adulthood and the results are validated by histological characterization of newly identified markers. This identifies seven neuron subgroups divided in two major branches of developing Pitx3-expressing neurons. Five of them express dopaminergic markers, while two express glutamatergic and GABAergic markers, respectively. Analysis also indicate evolutionary conservation of diversity in humans. This comprehensive molecular characterization will provide a valuable resource for elucidating mDA neuron subgroup development and function in the mammalian brain.</p>},
  articleno    = {581},
  author       = {Tiklová, Katarína and Björklund, Åsa K. and Lahti, Laura and Fiorenzano, Alessandro and Nolbrant, Sara and Gillberg, Linda and Volakakis, Nikolaos and Yokota, Chika and Hilscher, Markus M. and Hauling, Thomas and Holmström, Fredrik and Joodmardi, Eliza and Nilsson, Mats and Parmar, Malin and Perlmann, Thomas},
  issn         = {2041-1723},
  language     = {eng},
  month        = {02},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Single-cell RNA sequencing reveals midbrain dopamine neuron diversity emerging during mouse brain development},
  url          = {http://dx.doi.org/10.1038/s41467-019-08453-1},
  volume       = {10},
  year         = {2019},
}