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

Research output: Contribution to journalArticle

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 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.

Details

Authors
Organisations
External organisations
  • Uppsala University
  • Stockholm University
  • Karolinska Institutet
  • Ludwig Institute for Cancer Research, Stockholm branch
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
Original languageEnglish
Article number581
JournalNature Communications
Volume10
Issue number1
Publication statusPublished - 2019 Feb 4
Publication categoryResearch
Peer-reviewedYes