Long non-coding RNA repertoire and open chromatin regions constitute midbrain dopaminergic neuron - specific molecular signatures

Abstract

Midbrain dopaminergic (DA) neurons are involved in diverse neurological functions, including control of movements, emotions or reward. In turn, their dysfunctions cause severe clinical manifestations in humans, such as the appearance of motor and cognitive symptoms in Parkinson’s Disease. The physiology and pathophysiology of these neurons are widely studied, mostly with respect to molecular mechanisms implicating protein-coding genes. In contrast, the contribution of non-coding elements of the genome to DA neuron function is poorly investigated. In this study, we isolated DA neurons from E14.5 ventral mesencephalons in mice, and used RNA-seq and ATAC-seq to establish and describe repertoires of long non-coding RNAs (lncRNAs) and putative DNA regulatory regions specific to this neuronal population. We identified 1,294 lncRNAs constituting the repertoire of DA neurons, among which 939 were novel. Most of them were not found in hindbrain serotonergic (5-HT) neurons, indicating a high degree of cell-specificity. This feature was also observed regarding open chromatin regions, as 39% of the ATAC-seq peaks from the DA repertoire were not detected in the 5-HT neurons. Our work provides for the first time DA-specific catalogues of non-coding elements of the genome that will undoubtedly participate in deepening our knowledge regarding DA neuronal development and dysfunctions.