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Human photoreceptor cells from different macular subregions have distinct transcriptional profiles

ABSTRACT: Human photoreceptor cells from different macular subregions have distinct transcriptional profiles

PROVIDER: PRJNA714961 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13981700_1.fastq.gz	Fastqsanger.gz
	SRR13981700_2.fastq.gz	Fastqsanger.gz
	SRR13981701_1.fastq.gz	Fastqsanger.gz
	SRR13981701_2.fastq.gz	Fastqsanger.gz
	SRR13981702_1.fastq.gz	Fastqsanger.gz

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Human photoreceptor cells from different macular subregions have distinct transcriptional profiles [bulk RNA-seq]

Project description:Human photoreceptor cells from different macular subregions have distinct transcriptional profiles [bulk RNA-seq]

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Human photoreceptor cells from different macular subregions have distinct transcriptional profiles [single-cell RNA-seq]

Project description:Human photoreceptor cells from different macular subregions have distinct transcriptional profiles [single-cell RNA-seq]

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Human photoreceptor cells from different macular subregions have distinct transcriptional profiles [bulk RNA-seq]

Project description:Purpose: The goals of this study were to identify cell specific expression patterns from the fovea, perifovea, and macular neural retina. Methods: Independent libraries were prepared for human foveal (1mm), perifoveal (4mm), and macular (8mm) regions of neural retina. Poly-A selected RNA transcripts underwent 150 base-pair paired-end sequencing with an Illumina HiSeq 4000. Reads were mapped to the human genome hg19 with STAR (version = 020201) and quantified with the featureCounts function from the Rsubread package (version = 1.28.1). Differential expression analysis was performed with edgeR (version = 3.26.8). Results: Differential expression analysis identified genes enriched in each retinal region. Conclusions: This study provides a transcriptomic comparison of foveal, perifoveal, and macular human neural retina at the bulk and single-cell levels.

2021-05-13 | GSE169046 | GEO

Human photoreceptor cells from different macular subregions have distinct transcriptional profiles.

Project description:The human neural retina is a light sensitive tissue with remarkable spatial and cellular organization. Compared with the periphery, the central retina contains more densely packed cone photoreceptor cells with unique morphologies and synaptic wiring. Some regions of the central retina exhibit selective degeneration or preservation in response to retinal disease and the basis for this variation is unknown. In this study, we used both bulk and single-cell RNA sequencing to compare gene expression within concentric regions of the central retina. We identified unique gene expression patterns of foveal cone photoreceptor cells, including many foveal-enriched transcription factors. In addition, we found that the genes RORB1, PPFIA1 and KCNAB2 are differentially spliced in the foveal, parafoveal and macular regions. These results provide a highly detailed spatial characterization of the retinal transcriptome and highlight unique molecular features of different retinal regions.

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Human photoreceptor cells from different macular subregions have distinct transcriptional profiles [single-cell RNA-seq]

Project description:Purpose: The goals of this study were to identify expression patterns in foveal versus parafoveal cells isolated from the human retina. Methods: Independent libraries were prepared for foveal and parafoveal cells isolated from four human donors (donors 5-8). A foveal (1 mm) and parafoveal (4 mm) punch of neural retina was acquired from each donor. Each punch of neural retina was gently dissociated in papain (Worthington biochemical) for 1.25 hours before cryopreservation. Thawed cells were barcoded with the 10X chromium and resulting libraries were sequenced on an Illumina NovaSeq system. Sequenced reads were mapped to the human genome build GRCh38 with CellRanger(v3.0.1) and filtered to remove cells likely to be doublets or cells with a high proportion of mitochondrial reads. Libraries from single-cell donors 5-8 were aggregated using canonical correlation analysis. Feature selection was performed with the variance stabilizing transformation before integration was performed with Seurat (v3.0.1). Results: A total of 34,493 cells were recovered after filtering with 139,962,070 corresponding reads. A total of 5,856 cells were recovered from foveal libraries while 28,637 cells were recovered from the parafoveal libraries. Clusters were assigned to known retinal cell types based on expression of distinguishing marker genes. Differential expression analysis identified genes enriched in each population of cells originating from the fovea versus the parafovea. Particular emphasis was given to regionally expressed genes in cone photoreceptor cells and Muller cells. Conclusions: This study provides a transcriptomic comparison of the foveal and parafoveal human retina at the bulk and single-cell levels. The foveal retina is transcriptomically distinct from the directly surrounding parafovea.

2021-05-13 | GSE169047 | GEO

Human photoreceptor cells from different macular subregions have distinct transcriptional profiles

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-05-13 | GSE169048 | GEO

Distinct reward processing by subregions of the nucleus accumbens

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Loss of PILRB gene at age-related macular degeneration associated PILRB/PILRA locus impairs photoreceptor function in mouse retina

Project description:Genome-wide association studies have uncovered mostly non-coding variants at over 60 age- related macular degeneration (AMD) susceptibility loci. To ascertain the target gene at the PILRB/PILRA locus, we used a CRISPR strategy to produce germline deletions in the mouse paired immunoglobin-like type 2 receptor (Pilr) genes that encode highly related activating (PILRB) and inhibitory (PILRA) receptors. We show that a combined loss of Pilrb1 and Pilrb2, but not Pilra, leads to an early but relatively stationary defect in photoreceptor function without any apparent change in other retinal cells. PILRB immunostaining is specifically detected at the proximal part of photoreceptor outer segment. Reduced expression of select calcium-regulated phototransduction and synapse-associated proteins, including GCAP1 and 2, PDE6B, AIPL1, PSD95, and CTBP1, indicate dysregulation of calcium homeostasis as a possible mechanism of retinal phenotype in Pilrb1/2 -/- mice. Our studies suggest an association of PILRB, and not PILRA, with AMD pathogenesis.

2024-10-10 | GSE264349 | GEO

Distinct reward processing by subregions of the nucleus accumbens

Project description:The nucleus accumbens (NAc) plays an important role in motivation and reward processing. Recent studies suggest that different NAc subnuclei differentially contribute to reward-related behaviors. However, how reward is encoded in individual NAc neurons remains unclear. Using in vivo single-cell resolution calcium imaging, we discovered diverse patterns of reward encoding in the medial and lateral shell subdivision of the NAc (NAcMed and NAcLat, respectively). Reward consumption increases NAcLat activity but decreases NAcMed activity, albeit with high variability among neurons. The heterogeneity in reward encoding could be attributed to differences in their synaptic inputs and transcriptional profiles. Specific optogenetic activation of Nts-positive neurons in the NAcLat promotes positive reinforcement, while activation of Cartpt-positive neurons in the NAcMed induces behaviour aversion. Collectively, our study reveals organizational and transcriptional differences in NAc subregions, and provides a framework for future dissection of NAc subregions in physiological and pathological conditions.

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The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases

Project description:Primary and secondary cone photoreceptor cell death in retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, leads to severe vision impairment and blindness. Regardless of the fact that protection of cone photoreceptor cells under stress conditions, such as retinal degenerative diseases, is crucial for maintaining vision, the underlying molecular mechanisms are unclear. Here, we investigated the function of the deubiquitinase Otud7b/Cezanne in the retina. We identified that Otud7b is predominantly expressed in photoreceptor cells in the mouse retina. While the ablation of Otud7b did not cause a significant defect in development and maturation of the mouse retina, Otud7b‒/‒ mice subjected to light-induced damage, which is one of the dry age-related macular degeneration models, exhibited increased cone photoreceptor degeneration. In addition, Otud7b deficiency in Mak‒/‒ mice, a retinitis pigmentosa mouse model, resulted in further cone photoreceptor degeneration. Moreover, neuronal cells deficient in Otud7b were susceptible to serum starvation, resulting in cell death. We found that NF-κB activity is increased in the Otud7b‒/‒ retinas exposed to light by RNA-sequencing analysis. Luciferase reporter assay also demonstrated increased NF-κB activation in Otud7b-deficient neuronal cells under stress. The neuronal cell death resulting from Otud7b deficiency was suppressed through the inhibition of NF-κB. Furthermore, we observed that inhibition of NF-κB attenuated cone photoreceptor degeneration in the light-exposed Otud7b‒/‒ retina. Together, the current study suggests that Otud7b deubiquitinase protects cone photoreceptor cells under stress conditions by modulating the NF-κB activity.

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