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Identification of key regulatory pathways in response to long-term zinc supplementation in human primary retinal pigment epithelium: a multi-omics approach

ABSTRACT: Identification of key regulatory pathways in response to long-term zinc supplementation in human primary retinal pigment epithelium: a multi-omics approach

PROVIDER: PRJNA658007 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12475247.fastq.gz	Fastqsanger.gz
	SRR12475248.fastq.gz	Fastqsanger.gz
	SRR12475249.fastq.gz	Fastqsanger.gz
	SRR12475250.fastq.gz	Fastqsanger.gz
	SRR12475251.fastq.gz	Fastqsanger.gz

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Identification of key regulatory pathways in response to long-term zinc supplementation in human primary retinal pigment epithelium: a multi-omics approach

Project description:Purpose: In age-related macular degeneration (AMD), both systemic and local zinc concentrations are decreased. Elevating zinc levels by nutrition or oral supplementation has a positive impact on delaying the progression to end-stage AMD in clinical studies. Here we set out to identify key regulatory pathways involved in this beneficial effect in retinal pigment epithelial cells. Methods: Transcriptome profiles of 5 weeks old primary human fetal retinal pigment epithelial cells from 3 different donors were generated by RNA sequencing using Illumina NextSeq 5000. The samples from the 3 donors represent replicates of each conditions. The sequence reads that passed quality filters were analyzed further for differentially expressed genes (DEG) performing quasi-likelihood F-test in edgeR package (Robinson, McCarthy et al. 2010). Lowly expressed genes were filtered out using the following script was used: > keep <- rowSums(cpm(y)> 0.05) >= 1. To be considered as differentislly expressed gene, the Benjamini-Hochberg–adjusted P value was less than 0.05. Results: Using our data analysis workflow, we were able to identify over 32,000 transcripts. 826 of these were significantly changed in the three independent samples after apical and 218 after basal zinc supplementation when compared to untreated controls. Apical zinc supplementation upregulated 415 and down-regulated 411 transcripts. Basal zinc supplementation upregulated 157 and down-regulated 59 transcripts. 163 transcripts changed similarly after both apical and basal treatment.

2021-08-19 | GSE156452 | GEO

Identification of key regulatory pathways in response to long-term zinc supplementation in human primary retinal pigment epithelium: a multi-omics approachIdentification of key regulatory pathways in response to long-term zinc supplementation in human primary retinal pigment epithelium: a multi-omics approach

Project description:In age-related macular degeneration (AMD), both systemic and local zinc concentrations are decreased. Elevating zinc levels by nutrition or oral supplementation has a positive impact on delaying the progression to end-stage AMD in clinical studies. Here we set out to identify key regulatory pathways involved in this beneficial effect.

2021-09-09 | PXD020860 | Pride

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Project description:This is the proteomic analysis data of bovine retinal pigment epithelium cell lysate subjected to cryo-EM study.

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Project description:This SuperSeries integrates transcriptomic and epigenomic data generated from human retinal pigment epithelium. This SuperSeries is composed of the SubSeries listed below.

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Project description:The retinal pigment epithelium (RPE) provides vital support to photoreceptor cells and its dysfunction is associated with the onset and progression of age-related macular degeneration (AMD). Surgical provision of RPE cells may ameliorate AMD and thus it would be valuable to develop sources of patient-matched RPE cells for this application of regenerative medicine. We describe here the generation of functional RPE-like cells from fibroblasts that represent an important step toward that goal. We identified candidate master transcriptional regulators of RPEs using a novel computational method and then used these regulators to guide exploration of the transcriptional regulatory circuitry of RPE cells and to reprogram human fibroblasts into RPE-like cells. The RPE-like cells share key features with RPEs derived from healthy individuals, including morphology, gene expression and function, and thus represent a step toward the goal of generating patient-matched RPE cells for treatment of macular degeneration. Expression analysis was performed on induced retinal pigment epithelium-like cells.

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Project description:This is the first publication that assessed the complex molecular changes that underpin acute zinc supplementation-induced changes at the single cell RNA sequencing level in a well-characterised age-related macular degeneration (AMD) cell model. The retinal pigment epithelial (RPE) cells were allowed to mature for up to 19 weeks, during which time they developed sub-RPE deposits, a hallmark of AMD. Comparing the scRNA-Seq data from cells after two-, nine- and 19 weeks in culture, we identified distinct clusters of cells. Pseudotemporal ordering of the combined gene lists from all time points identified genes implicated in the dynamics of RPE cell differentiation, with enrichment in biologically plausible pathways. Acute (1 week) zinc supplementation (125 µM added zinc) resulted in the differential expression of several genes, including specific transcriptional regulators.

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