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

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

PROVIDER: PRJNA954737 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24143750_1.fastq.gz	Fastqsanger.gz
	SRR24143750_2.fastq.gz	Fastqsanger.gz
	SRR24143751_1.fastq.gz	Fastqsanger.gz
	SRR24143751_2.fastq.gz	Fastqsanger.gz
	SRR24143752_1.fastq.gz	Fastqsanger.gz

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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 [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

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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]

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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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Biphasic activation of WNT signaling enhances the derivation of midbrain dopamine neurons for translational use [ChIP-seq]

Project description:We report a novel midbrain dopamine neuron derivation protocol from human pluripotent stem cells (hPSC)s based on a two-step WNT signaling activation strategy. We perform genome-wide chromatin immunoprecipitation (ChIP-seq) for histone modifications including H3K4me3 and H3K27me3 with midbrain dopamine neuron differentiated cells from hPSC in Low-Chir and Boost-Chir (7.5 uM) conditions at day 11. Those results indicate that CHIR-boost promotes a more open chromatin structure at midbrain regions such as an EN1 locus based on increased H3K4me3 and decreased H3K27me3 levels. In contrast, analysis of the contaminating posterior (hindbrain) and anterior (diencephalic) lineage including NKX2-2 and PAX6 loci showed the opposite pattern with decreased H3K4me3 and increased H3K27me3 levels under CHIR-boost conditions. The protocol presented here is the basis for clinical grade dopamine neuron production and preclinical safety and efficacy studies.

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2020-12-18 | GSE162883 | GEO

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Project description:Midbrain dopamine (mDA) neurons constitute a heterogenous group of cells that have been intensely studied, not least because mDA neuron degeneration causes major symptoms in Parkinson’s disease. Diversity of mDA neurons has previously been well characterized anatomically but understanding diversity at a more complete molecular level has not previously been achieved. Here, we used single cell RNA sequencing of isolated mouse neurons expressing the transcription factor Pitx3, a marker for all types of mDA neurons. Analyses included cells isolated during development up until adulthood and was validated by histological characterization of newly identified markers. This characterization identified seven neuron subgroups divided in two major branches of developing Pitx3-expressing neurons. Five of these groups were dopaminergic, one glutamatergic and one GABAergic. Analyses also indicated evolutionary conservation of diversity in humans. This comprehensive molecular characterization will provide a molecular framework for further studies of the developing and mature mDA neuron subgroups in the mammalian brain.

2019-02-08 | GSE116138 | GEO

Single-cell RNA Sequencing Reveals Midbrain Dopamine Neuron Diversity Emerging During Mouse Brain Development

Project description:Single-cell RNA Sequencing Reveals Midbrain Dopamine Neuron Diversity Emerging During Mouse Brain Development

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