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Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE229488 | GEO | 2024/07/08

REPOSITORIES: GEO

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Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration

Project description:Midbrain dopamine (mDA) neurons play an essential role in cognitive and motor behaviours and are linked to different brain disorders. However, the molecular mechanisms underlying their development, and in particular the role of long non-coding RNAs (lncRNAs), remain incompletely understood. Here, we establish the transcriptomic landscape and alternative splicing patterns of linear and circular ncRNAs (lncRNAs and circRNAs) at key developmental timepoints in mouse mDA neurons using short and long-read RNAseq. Spatial analysis shows strong and subregion-specific expression of circRmst in mDA neurons and its post-transcriptional silencing affects soma size, TH+ neuron number, and mDA neuron positioning. Time-laps imaging indeed reveals that circRmst inhibits migration speed in developing mDA neurons. Together, these data for the first time establish a functional role for circRNAs in mDA neurons, further characterize poorly defined aspects of mDA neuron development, and provide a unique framework for future interrogation of lncRNAs in developing mDA neurons.

2024-07-08 | GSE229597 | GEO

Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration [circRMSTKD]

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Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration [time series]

Project description:Midbrain dopamine (mDA) neurons play an essential role in cognitive and motor behaviours and are linked to different brain disorders. However, the molecular mechanisms underlying their development, and in particular the role of long non-coding RNAs (lncRNAs), remain incompletely understood. Here, we establish the transcriptomic landscape and alternative splicing patterns of linear and circular ncRNAs (lncRNAs and circRNAs) at key developmental timepoints in mouse mDA neurons using RNAseq at different time points during early development. Spatial analysis shows strong and subregion-specific expression of circRmst in mDA neurons and its post-transcriptional silencing affects soma size, TH+ neuron number, and mDA neuron positioning. Time-laps imaging indeed reveals that circRmst inhibits migration speed in developing mDA neurons. Together, these data for the first time establish a functional role for circRNAs in mDA neurons, further characterize poorly defined aspects of mDA neuron development, and provide a unique framework for future interrogation of lncRNAs in developing mDA neurons.

2024-07-08 | GSE229481 | GEO

Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration

Project description:Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration

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Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration

Project description:Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration

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Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration [circRMSTKD]

Project description:Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration [circRMSTKD]

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Circular RNAs regulate neuron size and migration of midbrain dopamine neurons during development.

Project description:Midbrain dopamine (mDA) neurons play an essential role in cognitive and motor behaviours and are linked to different brain disorders. However, the molecular mechanisms underlying their development, and in particular the role of non-coding RNAs (ncRNAs), remain incompletely understood. Here, we establish the transcriptomic landscape and alternative splicing patterns of circular RNAs (circRNAs) at key developmental timepoints in mouse mDA neurons in vivo using fluorescence-activated cell sorting followed by short- and long-read RNA sequencing. In situ hybridisation shows expression of several circRNAs during early mDA neuron development and post-transcriptional silencing unveils roles for different circRNAs in regulating mDA neuron morphology. Finally, in utero electroporation and time-lapse imaging implicate circRmst, a circRNA with widespread morphological effects, in the migration of developing mDA neurons in vivo. Together, these data for the first time suggest a functional role for circRNAs in developing mDA neurons and characterise poorly defined aspects of mDA neuron development.

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Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration [time series]

Project description:Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration [time series]

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

Project description: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.

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A multifunctional locus controls motor neuron differentiation through short and long non coding RNAs

Project description:The transition from dividing progenitors to post-mitotic motor neurons (MNs) is orchestrated by a series of events, which are mainly studied at the transcriptional level by analyzing the activity of specific programming transcription factors. Here, we identify a post-transcriptional role of a MN-specific transcriptional unit (MN2) harboring a lncRNA (lncMN2-203) and two miRNAs (miR-325-3p and miR-384-5p) in this transition. Through the use of in vitro mESC differentiation and single-cell sequencing of CRISPR/Cas9 mutants, we demonstrate that lncMN2-203 affects MN differentiation by sponging miR-466i-5p and up-regulating its targets, including several factors involved in neuronal differentiation and function. In parallel, miR-325-3p and miR-384-5p, co-transcribed with lncMN2-203, act by repressing proliferation-related factors. These findings indicate the functional relevance of the MN2 locus and exemplify additional layers of specificity regulation in MN differentiation.

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