Transcriptional Profiling Provides New Insights into Organ Culture-Induced Changes in Human Donor Corneas
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ABSTRACT:
PROVIDER: PRJNA887398 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21814856.fastq.gz | Fastqsanger.gz | |||
| SRR21814857.fastq.gz | Fastqsanger.gz | |||
| SRR21814858.fastq.gz | Fastqsanger.gz | |||
| SRR21814859.fastq.gz | Fastqsanger.gz | |||
| SRR21814860.fastq.gz | Fastqsanger.gz |
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Project description:Corneal transplantation is one of the most common forms of tissue transplantation worldwide. Donor corneal tissue used in transplantation is provided by eye banks, which store the tissue in culture medium after procurement. To date, the effects of cell culture on human corneal tissue have not been fully elucidated. Using the 3’ RNA sequencing method for massive analysis of cDNA ends (MACE), we show that cultivation of corneal tissue leads to significant changes in a variety of molecular processes in human corneal tissue that go well beyond aspects of previously known culture effects. Functionally grouped network analysis revealed nine major groups of biological processes that were affected by corneal organ culture, among them keratinization, hypoxia, and angiogenesis, with genes from each group being affected by culture time. A cell type deconvolution analysis revealed significant modulations of the corneal immune cell profile in a time dependent manner. The results suggest that current culture conditions should be further refined and that prolonged cultivation may be detrimental. Recently, we showed that MACE enables transcrip-tional profiling of formalin-fixed and paraffin-embedded (FFPE) conjunctival tissue with high accuracy even after more than 10 years of storage. Here we demonstrate that MACE provides comparable results for native and FFPE corneal tissue, confirming that the technology is suitable for transcriptome analysis of a wide range of archived diseased corneal samples stored in histo-logical archives. Finally, our data underscore the feasibility of bioinformatics cell-type enrich-ment analysis in bulk RNA-seq data to profile immune cell composition in fixed and archived corneal tissue samples, for which RNA-seq analysis of individual cells is often not possible.
2022-11-22 | GSE214853 | GEO
Project description:Purpose: We compared the levels of miRNA specific for DEGs in isograft corneas with those in normal corneas, as well as the levels of miRNA specific for DEGs in allograft corneas with those in isograft corneas, to gain a better understanding of molecular variables that affect corneal graft rejection pathways. Methods: Illumina Hiseq 2500 deep sequencing was used to screen for differentially expressed genes (DEGs) in matched pairs of isograft corneas and normal corneas, allograft corneas and isograft corneas. Potential target genes among the DEGs were predicted using target prediction software (TargetScan, Miranda, miRDB, and CLIP), and the overlay portion was analyzed using the Gene Ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG). An analysis of the interactions between DEG proteins (PPI analysis) and a MetaCore software analysis. Results: Our results showed that 22 miRNAs were significantly upregulated and 4 were significantly downregulated in the isograft group when compared with the control group (P < 0.01), while 17 miRNAs were significantly upregulated and 3 were significantly downregulated in the allograft group when compared with the isograft group (P < 0.01). Among the miRNAs with altered expression levels, miR-155-5p, miR-142-3p, miR-142-5p, and miR-223-3p displayed simultaneous changes in the above two comparisons. Potential target genes among the DEGs were predicted using target prediction software, and the overlay portion was analyzed using the Gene Ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG). GO and KEGG analyses showed that the DEGs were mainly involved in metabolic pathways, cytokine secretion, and tumor immunity functions. An analysis of the interactions between DEG proteins (PPI analysis) and a MetaCore software analysis of 4 key DEGs revealed that the genes regulated by miR-155-5p played important roles in the miRNA-mRNA regulatory network. Furthermore, the MetaCore analysis identified C/EBP beta, p53, and sp1 as key transcription factors in that network. Conclusions: Our study identified transplanted corneas-specific miRNA in matched pairs of isograft corneas and normal corneas, allograft corneas and isograft corneas. Furthermore, bioinformatics analysis of the key miRNA regulatory network revealed the molecular mechanisms, which suggests miRNAs may as new molecular targets for treating corneal injuries and corneal transplant rejection
2018-04-28 | GSE113787 | GEO
Project description:Background: Strategies to improve long term renal allograft survival have been directed to recipient dependent mechanisms of renal allograft injury. In contrast, no such efforts have been made to optimize organ quality in the donor. In order to get insight into the deleterious gene pathways expressed at different time points during deceased kidney transplantation, transcriptomics was performed on kidney biopsies from a large cohort of deceased kidney transplants. Methods: A total of 554 kidney biopsies were taken from living and deceased donor kidneys at donation, after cold ischemia and after reperfusion. Transcriptomics by means of whole genome micro-array analyses followed by functional pathway analyses was performed. Results: Oxidative stress and complement- and coagulation pathways were uncovered as potential pathways for intervention in deceased donors. No genes were found to be differentially expressed between donation and cold ischemia. After reperfusion, pathways related to oxidative stress, NOD-like signalling, MAPK, cytokine-cytokine receptor, complement- and-coagulation and chemokines were enriched in kidneys from deceased organ donors. Pathways related to prolonged and worsening deprivation of oxygen were associated with delayed graft function of DCD grafts. Conclusions: The present study reveals oxidative stress and enrichment of complement and coagulation pathways in deceased donor kidneys. Future intervention therapies to optimize donor organ quality and prolong allograft survival should target oxidative stress and innate immune activation in the donor.
2015-04-02 | GSE43974 | GEO
Project description:Characteristic structural details of the cornea are transparency, the absence of blood vessels, and the presence of numerous sensory nerve endings. The corneal epithelium is one of the most densely innervated tissues of the body. The characteristics of the cornea are established during fetal development, and are lost in adult life when the cornea regenerates after injury. The common reaction of the cornea to injury is the formation of opaque scars, the ingrowth of blood vessels, and distinct changes in the innervation pattern. Scar formation of the cornea is critically modulated by the expression of transforming growth factor-beta (TGF-beta). To identify genes that are important for corneal transparency, dense innervation and absence of blood vessels by comparing corneas from wildtype mice with those that are under the influence of high doses of TGF-beta. Transparency, dense innervation, and absence of blood vessels in the cornea all depend on the expression of a critical set of genes that are not expressed when TGF-beta is present. Mice were generated that overexpress TGF-beta under control of a strong lens-specific promoter. These mice developed opaque corneas that are vascularized and lack sensory nerves. In addition, these corneas were densely populated with cells expressing neural cell adhesion protein. RNA was isolated from corneas of transgenic animals and wildtype littermates in order to analyze differentially expressed genes and to identify those that are only expressed in transparent, avascular, and densely innervated wildtype corneas.
2008-06-15 | E-GEOD-6676 | biostudies-arrayexpress
Project description:Determinion of performance of a molecular marker panel - derived via a systems biology data integration approach reflecting renal transplant pre-implantation donor organ status - to predict post-transplant renal function in an independent cohort.
2018-05-04 | GSE95026 | GEO
Project description:Donor organ shortage, growing waiting lists and organ discard rates are key problems in kidney transplantation. Donor organ quality is a critical factor determining post-transplant graft outcomes. However, organ quality is difficult to predict. Balancing the use of marginal donors without affecting outcomes is a main issue in the transplant field. The decision of acceptance of a kidney organ for transplantation is mainly based on donor organ biopsy findings, even though there are recognized limitations. The lack of better measures of organ quality at the time of transplantation as a predictor of performance graft outcome is a serious clinical challenge. Herein, we propose the use of a limited set of genes that captures intrinsic biology of kidney donor organs to improve available scoring systems. We studied gene expression in 192 deceased donor kidney biopsies and evaluated short-term outcomes which included delayed graft function and eGFR (high versus low) at 24 months for 168 kidney transplant recipients.
2022-06-13 | GSE147451 | GEO
Project description:BackgroundIndividuals who have failed one or more full thickness penetrating keratoplasties may be offered repeat corneal surgery using an artificial or donor cornea. An artificial or prosthetic cornea is known as a keratoprosthesis. Both donor and artificial corneal transplantations involve removal of the diseased and opaque recipient cornea (or the previously failed cornea) and replacement with another donor or prosthetic cornea.ObjectivesTo assess the effectiveness of artificial versus donor corneas in individuals who have had one or more failed donor corneal transplantations.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 11); Ovid MEDLINE; Ovid Embase; LILACS (Latin American and Caribbean Health Sciences Literature database); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 4 November 2019.Selection criteriaTwo review authors independently assessed reports from the electronic searches to identify randomized controlled trials or controlled clinical trials. Any discrepancies were resolved by discussion or consultation.Data collection and analysisWe used standard methodological procedures expected by Cochrane. For discussion purposes, we summarized findings from relevant comparative case series. We performed no data synthesis.Main resultsWe did not identify any randomized controlled trials or controlled clinical trials comparing artificial corneas with donor corneas for repeat corneal transplantations.Authors' conclusionsThe optimal management for those individuals who have failed a conventional corneal transplantation is unknown. Currently, in some centers, artificial corneal devices are routinely recommended after just one graft failure, while in other centers, they are not recommended until after multiple graft failures, or not at all. To date, there have been no controlled trials comparing the visual outcomes and complications of artificial corneal devices (particularly the Boston type 1 keratoprosthesis, which is the most commonly implanted artificial corneal device) with repeat donor corneal transplantation, in order to guide surgeons and their patients. Such a trial is needed and would offer significant benefit to an ever-increasing pool of people with visual disability due to corneal opacification, most of whom are still in productive stages of their lives.
| S-EPMC7388900 | biostudies-literature
Project description:Comparative transcriptome between Keratoconus and control corneas
2011-08-17 | E-MEXP-2777 | biostudies-arrayexpress
Project description:The objective of this study was to analyze gene expression associated to the process of cell and tissue differentiation of bioengineered human anterior lamelar corneas We used microarrays to detail the global programme of gene expression associated to bioengineered corneas differentiation
2016-09-09 | GSE86584 | GEO
Project description: Not available
| S-EPMC11235244 | biostudies-literature