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Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins

ABSTRACT: Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins

PROVIDER: PRJNA769144 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16227586.fastq.gz	Fastqsanger.gz
	SRR16227587.fastq.gz	Fastqsanger.gz
	SRR16227588.fastq.gz	Fastqsanger.gz
	SRR16227589.fastq.gz	Fastqsanger.gz
	SRR16227590.fastq.gz	Fastqsanger.gz

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Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins

Project description:To determine the molecular differences between ventral Sox6+ and dorsal Sox6- DA neurons, we performed bulk RNA-sequencing in sorted mCherry+ and GFP+ cells from the SNc of adult Sox6-FSF-Cre, Th-2A-Flpo, RC-Frepe mice. Our analysis revealed large and significant differential gene expression between these two populations.

2021-10-27 | GSE185480 | GEO

Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins.

Project description:Dopamine (DA) neurons in the ventral tier of the substantia nigra pars compacta (SNc) degenerate prominently in Parkinson's disease, while those in the dorsal tier are relatively spared. Defining the molecular, functional, and developmental characteristics of each SNc tier is crucial to understand their distinct susceptibility. We demonstrate that Sox6 expression distinguishes ventrally and dorsally biased DA neuron populations in the SNc. The Sox6+ population in the ventral SNc includes an Aldh1a1+ subset and is enriched in gene pathways that underpin vulnerability. Sox6+ neurons project to the dorsal striatum and show activity correlated with acceleration. Sox6- neurons project to the medial, ventral, and caudal striatum and respond to rewards. Moreover, we show that this adult division is encoded early in development. Overall, our work demonstrates a dual origin of the SNc that results in DA neuron cohorts with distinct molecular profiles, projections, and functions.

| S-EPMC8607753 | biostudies-literature

Transcriptomic profiling of mouse substantia nigra tissue by RNA-seq

Project description:Transcriptomic profiling of substantia nigra of wild type (WT) and Tpbg knockout (KO) mice (RNA-seq)

2021-12-01 | GSE178400 | GEO

Proteomic analysis of substantia nigra

Project description:Proteomic analysis of human substantia nigra using protein and peptide fractionations strategies coupled to nanoLC-MS/MS

2015-08-17 | PXD001496 | Pride

Control human putamen and Substantia Nigra

Project description:The study is affiliated to the UKBEC sample of healthy human putamen and substantia nigra phenotype. The gender is from both male and female samples of the the phenotype.

| EGAS00001003065 | EGA

Time Course of Gene Expression in the Substantia Nigra in Response to Intrastriatal 6-hydroxydopamine in the rat.

2014-06-21 | GSE58710 | GEO

Time Course of Gene Expression in the Substantia Nigra in Response to Intrastriatal 6-hydroxydopamine in the rat.

Project description:The 6-hydroxydopamine (6OHDA) rat model of parkinsonism is among the first, and most commonly used, animal models of Parkinson’s disease. It provides insight into the compensatory changes that occur in the brain after dopamine (DA) neuron degeneration. In order to better define the consequences of substantia nigra DA neuron loss on the neural and glial populations during and following nigrostriatal degeneration, tissue was collected and evaluated from the substantia nigra of 6OHDA or vehicle treated, or naïve rats at 1, 2, 4, 6 & 16 weeks. Comprehensive gene expression analysis was conducted to detect significant differences in gene expression. Comparisons were conducted within the same treatment groups over time as well as across treatments within the same post-treatment interval. Longitudinal expression patterns were parsed using a k-means clustering algorithm as a method for finding patterns indicative of neuronal loss, upregulation in response to lesion or surgical damage exclusive of lesion. Tissue was collected from the substantia nigra of 6OHDA treated, sham and naïve rats at 1, 2, 4, 6 & 16 weeks post-treatment. A unilateral striatal lesion was employed that results in a 99% striatal DA reduction and an 80% loss of DA neurons in the substantia nigra. 6OHDA lesions were confirmed via catecholamine quantitation by HPLC. RNA integrity was assessed with an Agilent 2100 Bioanalyzer with minimum RIN acceptance criteria of 8.0. Multidimensional plots and Pearson Correlations were used to establish group/treatment homogeneity. Tissue was subjected to comprehensive gene expression analysis using the Affymetrix Rat Gene 1.0ST array.

2014-06-21 | E-GEOD-58710 | biostudies-arrayexpress

Age-mediated transcriptomic changes in adult mouse substantia nigra

Project description:Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques. Here, aging-associated early changes in transcriptome of SNpc were investigated comparing late middle-aged (18 months old) to young (2 months old) mice.

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Transcriptomic profiling of substantia nigra and putamen in Parkinson’s disease

Project description:We report RNA sequencing results of human substantia nigra and putamen samples from Parkinson's disease patients and controls. Each substantia nigra sample is the result of pooling brain tissue from two individuals with the same , while each putamen sample is the result of pooling brain tissue from three individuals. We found 354 differentially expressed genes (DEGs) in the SN of PD patients compared to age-matched controls, while we observed 261 DEGs in the putamen samples. The top-enriched pathways from the SN were associated with “protein folding” and “neurotransmitter transport”, and the putamen DEGs with “synapse organization”. In summary, our data confirms the key role of protein folding and neuronal degeneration in the pathology of PD, and highlights new genes and pathways that have not yet been explored in the context of PD.

2020-09-02 | GSE136666 | GEO

Gene expression profiling of substantia nigra: a post-mortem study in Parkinson's disease and control subjects

Project description:Introduction: Parkinson's disease (PD) is characterized by bradykinesia, tremor, and rigidity; in addition, postural instability sets in as the disease progresses. Non-motor symptoms of the disease include cognitive, behavioral, and neuropsychiatric changes, sensory and sleep disturbances that may precede the motor symptoms of the disease itself. The peculiar pathological features of PD are decreased dopaminergic neurons and dopamine levels in the substantia nigra pars compacta and pontine locus ceruleus. The study of the transcriptome plays a major role in the identification of genes and gene regulatory mechanisms in multifactorial neurodegenerative diseases such as Parkinson's disease itself. Therefore, we proposed to study the transcriptome directly in the midbrain containing the "Substantia nigra.The study was performed in 8 subjects with PD and 6 normal control subjects, using next-generation sequencing (NGS) technologies. Results: With the use of an ad hoc bioinformatics pipeline, gene expression profiles in the different PD subjects were obtained and compared to those of controls. In detail, the results obtained from the data analysis indicated 92 differentially expressed genes (FDR-adjusted p value ≤0.05 and fold-change less than -1.5 or greater than +1.5) of which 33 genes were up-regulated while 59 were down-regulated. Conclusions: Functional analysis of the differentially expressed genes revealed several genes involved in different canonical pathways indicating their likely significant role in Parkinson's disease.

2024-01-03 | E-MTAB-13295 | biostudies-arrayexpress

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