The transcriptional landscape of dopaminergic cells

Mesencephalic dopaminergic neurons present two major groups of projecting cells: the A9 neurons of the Substantia Nigra (SN) and the A10 cells of the Ventral Tegmental Area (VTA). In PD A9 cells degenerate while A10 neurons are relatively spared. In the last years we have been aiming to describe their transcriptomes to study the biology of dopaminergic cells and unveil the molecular basis of their selective vulnerability. Since any meaningful description of gene expression must comprise the detection of lncRNAs and repetitive sequences, we have been taking advantage of nanoCAGE. Dopaminergic neurons have thus been purified with Laser Capture Microdissection from a transgenic mouse line where dopaminergic cells were labeled with the Green Fluorescent Proteins. nanoCAGE libraries were then synthesized and sequenced. We have been thus able to define and quantify the Transcription Start Site usage of ex-vivo dopaminergic neurons in a genome-wide scale. This work is allowing us to answer to the long-standing question on how the transcriptome of a specific neuronal cell type is structured in terms of protein coding genes, lncRNAs, repetitive elements and antisense transcription.