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

Katarína Tiklová (), Åsa K. Björklund, Laura Lahti, Alessandro Fiorenzano, Sara Nolbrant, Linda Gillberg, Nikolaos Volakakis, Chika Yokota, Markus M. Hilscher, Thomas Hauling, Fredrik Holmström, Eliza Joodmardi, Mats Nilsson, Malin Parmar and Thomas Perlmann ()
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Katarína Tiklová: Ludwig Institute for Cancer Research
Åsa K. Björklund: Uppsala University
Laura Lahti: Ludwig Institute for Cancer Research
Alessandro Fiorenzano: Lund University
Sara Nolbrant: Lund University
Linda Gillberg: Ludwig Institute for Cancer Research
Nikolaos Volakakis: Ludwig Institute for Cancer Research
Chika Yokota: Stockholm University
Markus M. Hilscher: Stockholm University
Thomas Hauling: Stockholm University
Fredrik Holmström: Ludwig Institute for Cancer Research
Eliza Joodmardi: Ludwig Institute for Cancer Research
Mats Nilsson: Stockholm University
Malin Parmar: Lund University
Thomas Perlmann: Ludwig Institute for Cancer Research

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08453-1

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