Transcriptome of Human Primary Corneal Endothelial Cells with SLC4A11 deficiency
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA597782 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10769312_1.fastq.gz | Fastqsanger.gz | |||
| SRR10769312_2.fastq.gz | Fastqsanger.gz | |||
| SRR10769313_1.fastq.gz | Fastqsanger.gz | |||
| SRR10769313_2.fastq.gz | Fastqsanger.gz | |||
| SRR10769314_1.fastq.gz | Fastqsanger.gz |
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Project description:Mutations in the solute-linked carrier family 4 member 11 (SLC4A11) gene are associated with several corneal endothelial dystrophies, in all of which visually significant cornea edema may require corneal transplantation. To elucidate the pathogenesis of SLC4A11 associated corneal endothelial dystrophies, we analyzed the transcriptome of SLC4A11 knock-down primary human corneal endothelium (SLC4A11 KD pHCEnC) and scrambled RNA treated pHCEnC as controls.
2020-08-13 | GSE142636 | GEO
Project description:Mutations in the solute-linked carrier family 4 member 11 (SLC4A11) gene are associated with several corneal endothelial dystrophies, in all of which visually significant cornea edema may require corneal transplantation. To elucidate the pathogenesis of SLC4A11 associated corneal endothelial dystrophies, we analyzed the transcriptome of immortalized mouse corneal endothelial cells (Slc4a11-/- MCEnC) and Slc4a11+/+ MCEnC as controls.
2020-08-13 | GSE142635 | GEO
Project description:Transcriptome of Immortalized Mouse Corneal Endothelial Cells with SLC4A11 deficiency
| PRJNA597783 | ENA
Project description:Sex differences have been described in several corneal diseases such as Fuchs endothelial corneal dystrophy and keratoconus, with estrogens implicated in the induction of these differences. Here, we report the identification of sex differences in a cohort of 161 individuals with Corneal Hereditary Endothelial Dystrophy (CHED), a rare corneal endothelial dystrophy associated with biallelic SLC4A11 gene mutations, and in a Slc4a11-/- mouse model of CHED. Male sex is associated with more severe corneal edema, the characteristic clinical feature of CHED, in affected individuals and Slc4a11-/- mice. The corneal endothelium in male Slc4a11-/- mice demonstrates increased levels of oxidative stress compared to female mice, evidenced by age-dependent higher levels of glucose- and glutamine-derived mitochondrial superoxide. Removal of gonadal hormones in Slc4a11-/- mice via gonadectomy increases corneal edema in female mice, suggesting a protective role for ovarian hormones. Transcriptomic analysis of corneal endothelium and body composition analysis in Slc4a11+/+ and Slc4a11-/- mice suggest that estrogens play a role in promoting corneal endothelial utilization of lipids via β-oxidation as an alternative energy source in the setting of decreased SLC4A11, thereby reducing oxidative stress from glucose and glutamine metabolism.
2026-05-15 | GSE288029 | GEO
Project description:Purpose: Slc4a11 KO mice show significant edema and altered corneal endothelial morphology at an early age with concomitant increased mitochondrial ROS and oxidative damage relative to wild type. Here we used RNA-Seq with the goal of finding pathways related to corneal endothelial metabolic, pump and barrier function alterations. Methods: Corneal endothelium-Descemet’s membrane (CEDM) samples were from WT and Slc4a11 KO mice at 12 weeks of age. RNA sequencing data was subjected to Ingenuity Pathway Analysis and QPCR for validation. Results: The RNA sequencing IPA analysis predicted activation, inhibition or differential regulation of several pathways. We validated downregulation of Glycolytic enzymes, Mitochondrial complex components and Ion transporters. We observed upregulation of genes of cholesterol biosynthesis, GSH metabolism and tight and adherens junctions. Conclusions: Slc4a11 KO induces a coordinated decrease in glycolysis, glutaminolysis, oxygen consumption, lactate transporters and Na-K-ATPase. These changes together with the altered barrier function cause an accumulation of stromal lactate in Slc4a11 KO mice leading to chronic corneal edema.
2022-02-02 | GSE174586 | GEO
Project description:Considerable interest has been generated for the development through cell-tissue engineering of suitable corneal endothelial graft alternatives, which can potentially alleviate the shortage of corneal transplant material. The advent of less invasive suture-less key-hole surgery options such as DescemetM-bM-^@M-^Ys Stripping Endothelial Keratoplasty (DSEK) and DescemetM-bM-^@M-^Ys Membrane Endothelial Keratoplasty (DMEK), which involve transplantation of solely the endothelial layer instead of full thickness cornea, provide further impetus for the development of alternative endothelial grafts for clinical applications. A major challenge for this endeavor is the lack of specific markers for this cell type. To identify genes that reliably mark corneal endothelial cells (CECs) in vivo and in vitro, we performed RNA-sequencing on freshly isolated human CECs (from both young and old donors), CEC cultures, and corneal stroma. Gene expression of these corneal cell types were also compared to that of other human tissue types. Based on high throughput comparative gene expression analysis, we identified a panel of markers that are: i) highly expressed in CECs from both young donors and old donors; ii) expressed in CECs in vivo and in vitro; and iii) not expressed in corneal stroma keratocytes and the activated corneal stroma fibroblasts. These were SLC4A11, COL8A2 and CYYR1. The use of this panel of genes in combination reliably ascertains the identity of the CEC cell type. A total of 20 donor corneas consisting of 10 single donor corneas and 5 paired donor corneas were used in this study. Donor age ranged from 19 - 76. This RNA-seq study included 15 pooled corneas (5 each) used form CEC old, CEC young and stroma samples.
2013-05-23 | E-GEOD-44064 | biostudies-arrayexpress
Project description:Considerable interest has been generated for the development through cell-tissue engineering of suitable corneal endothelial graft alternatives, which can potentially alleviate the shortage of corneal transplant material. The advent of less invasive suture-less key-hole surgery options such as Descemet’s Stripping Endothelial Keratoplasty (DSEK) and Descemet’s Membrane Endothelial Keratoplasty (DMEK), which involve transplantation of solely the endothelial layer instead of full thickness cornea, provide further impetus for the development of alternative endothelial grafts for clinical applications. A major challenge for this endeavor is the lack of specific markers for this cell type. To identify genes that reliably mark corneal endothelial cells (CECs) in vivo and in vitro, we performed RNA-sequencing on freshly isolated human CECs (from both young and old donors), CEC cultures, and corneal stroma. Gene expression of these corneal cell types were also compared to that of other human tissue types. Based on high throughput comparative gene expression analysis, we identified a panel of markers that are: i) highly expressed in CECs from both young donors and old donors; ii) expressed in CECs in vivo and in vitro; and iii) not expressed in corneal stroma keratocytes and the activated corneal stroma fibroblasts. These were SLC4A11, COL8A2 and CYYR1. The use of this panel of genes in combination reliably ascertains the identity of the CEC cell type.
2013-05-23 | GSE44064 | GEO
Project description:Human corneal endothelial cells (HCEC) form a monolayer by adhering tightly through their intercellular adhesion molecules. Located at the posterior corneal surface, they maintain corneal translucency by dehydrating the corneal stroma, mainly through the Na+- and K+-dependent ATPase (Na+/K+-ATPase). Because HCEC proliferative activity is low in vivo,we tried to activate proliferation of HCEC by inhibiting cyclin-dependent kinase inhibitors.We have here demonstrated microarray data of transduced human corneal endothelial cell lines. Affymetrix human U133 plus 2.0 array was used to transcriptionally profile to compare cultured human corneal endothelial cells and transduced human corneal endothelial cells.
2011-10-29 | E-GEOD-30781 | biostudies-arrayexpress
Project description:The corneal endothelium plays a primary role in maintaining corneal homeostasis and clarity, and must be surgically replaced with allogenic donor corneal endothelium in the event of visually significant dysfunction. However, a worldwide shortage of donor corneal tissue has led to a search for alternative sources of transplantable tissue. Cultured human corneal endothelial cells (HCEnC) have been shown to restore corneal clarity in experimental models of corneal endothelial dysfunction in animal models, but characterization of cultured HCEnC remains incomplete. To this end, we utilized next-generation RNA sequencing technology to compare the transcriptomic profile of ex vivo human corneal endothelium (evHCEnC) with that of primary HCEnC and HCEnC lines, and to determine the utility of cultured and immortalized corneal endothelial cells as models of in vivo corneal endothelium. Multidimensional analyses of the transcriptome datasets demonstrated that primary HCEnC have a closer relationship to evHCEnC than do immortalized HCEnC. Subsequent analyses showed that the majority of the genes specifically expressed in HCEnC (not expressed in ex vivo corneal epithelium or fibroblasts) demonstrated a marked variability of expression in cultured cells compared with evHCEnC. In addition, genes associated with either corneal endothelial cell function or corneal endothelial dystrophies were investigated. Significant differences in gene expression and protein levels were observed in the cultured cells compared with evHCEnC for each of the genes tested except for AGBL1 and LOXHD1, which were not detected by RNA-seq or qPCR. Our transcriptomic analysis suggests that at a molecular level primary HCEnC most closely resemble evHCEC and thus represent a viable therapeutic option for managing corneal endothelial dysfunction. Our findings also suggest that investigators should perform an assessment of the entire transcriptome of cultured HCEnC prior to determination of the potential clinical utility of the cultured HCEnC for the management of corneal endothelial cell failure. Transcriptomes from ex vivo corneal endothelium, primary cultures and three cell lines were compared. Three samples of each endothelial cell group were submitted for RNA sequencing for a total of 15 samples. The transcriptome for the ex vivo corneal endothelium was used as the reference (i.e., proxy for in vivo corneal endothelium). Transcript abundances for a subset of genes associated with corneal endothelial cell function or disease were validated with qPCR and western blot. Samples of ex vivo endothelium used for validation were independent replicates not used for RNA-sequencing.
2015-09-04 | E-GEOD-65991 | biostudies-arrayexpress
Project description:This dataset contains proteomic profiles of Descemet's membrane (DM) with corneal endothelial cells derived from patients with Fuchs endothelial corneal dystrophy (FECD) and non-FECD subjects by shotgun proteomics. FECD is the most common inherited corneal disease. Fibrillar focal excrescences, called guttae, and corneal edema due to corneal endothelial cell death result in progressive vision loss. Our dataset indicated that 32 distinctive molecules were expressed only in the FECD-DM but not in the DM of the control subject, possibly having important roles in the pathophysiology of FECD.
2023-01-17 | MSV000091078 | MassIVE