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

• DOI: 10.1038/s41467-019-08453-1
• Publication Date: 2019-02-04T11:04:09Z
• Authors: Katarína Tiklová; Åsa K. Björklund; Laura Lahti; Alessandro Fioren...; Sara Nolbrant; Linda Gillberg; Nikolaos Volakakis; Chika Yokota; Markus M. Hilscher; Thomas Hauling; Fredrik Holmström; Eliza Joodmardi; Mats Nilsson; Malin Parmar; Thomas Perlmann
• Keywords: Homeodomain Proteins; 0303 health sciences; Sequence Analysis, RNA; Cell- och molekylärbiologi; Science; Dopaminergic Neurons; Q; Neurosciences; Brain; Gene Expression Regulation, Developmental; Article; Mice; 03 medical and health sciences; Animals; Neurovetenskaper; Cell and Molecular Biology; Transcription Factors

AbstractMidbrain 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.