Injury response of human lens epithelial cells ex-vivo
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE186716 | GEO | 2024/10/27
REPOSITORIES: GEO
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Project description:Mutations in Peroxidasin (PXDN) cause severe inherited eye disorders in humans, such as congenital cataract, corneal opacity, and developmental glaucoma. The role of peroxidasin during eye development is poorly understood. Here we describe the first Pxdn mouse mutant which was induced by ENU (N-ethyl-N-nitrosourea) and led to a recessive phenotype. Sequence analysis of cDNA revealed a T3816A mutation resulting in a premature stop codon (Cys1272X) in the peroxidase domain. This mutation causes severe anterior segment dysgenesis and microphthalmia resembling the manifestations in patients with PXDN mutations. The proliferation and differentiation of the lens is disrupted in association with aberrant expression of transcription factor genes (Pax6 and Foxe3) in mutant eyes. Additionally, Pxdn is involved in the consolidation of the basement membrane and lens epithelium adhesion in the ocular lens. Lens material including γ-crystallin is extruded into the anterior and posterior chamber due to local loss of structural integrity of the lens capsule as a secondary damage to the anterior segment development leading to congenital ocular inflammation. Moreover, Pxdn mutants exhibited an early-onset glaucoma and progressive retinal dysgenesis. Transcriptome profiling revealed that peroxidasin affects the transcription of developmental and eye diseases-related genes at early eye development. These findings suggest that peroxidasin is necessary for cell proliferation and differentiation and for basement membrane consolidation during eye development. Our studies provide pathogenic mechanisms of PXDN mutation-induced congenital eye diseases.
2014-05-02 | GSE49704 | GEO
Project description:The eye lens is composed of fiber cells, which differentiate from epithelial cells on its anterior surface. In concert with this differentiation, a set of proteins essential for lens function is synthesized, and the cellular organelles are degraded. To understand the molecular mechanism of the lens cell differentiation, we compared the gene expression profiles between epithelial and cortical fiber cells of young mouse lens using a microarray analysis. Keywords: cell-type comparison
2007-08-01 | GSE7533 | GEO
Project description:The mature eye lens contains a surface layer of epithelial cells called the lens epithelium that require a functional mitochondrial population to maintain the homeostasis and transparency of the entire lens. The lens epithelium overlies a core of terminally differentiated fiber cells that must degrade their mitochondria to achieve lens transparency. These distinct mitochondrial populations make the lens a useful model system to identify those genes that regulate the balance between mitochondrial homeostasis and elimination. Here we used an RNA sequencing and bioinformatics approach to identify the transcript levels of all genes expressed by distinct regions of the lens epithelium and maturing fiber cells of the embryonic Gallus gallus (chicken) lens. Our analysis detected over 15,000 unique transcripts expressed by the embryonic chicken lens. Of these, over 3000 transcripts exhibited significant differences in expression between lens epithelial cells and fiber cells. Multiple transcripts coding for separate mitochondrial homeostatic and degradation mechanisms were identified to exhibit preferred patterns of expression in lens epithelial cells that require mitochondria relative to lens fiber cells that require mitochondrial elimination. These included differences in the expression levels of metabolic, autophagy, and mitophagy transcripts between lens epithelial cells and lens fiber cells. These data provide a comprehensive window into all genes transcribed by the lens and those mitochondrial regulatory and degradation pathways that function to maintain mitochondrial populations in the lens epithelium and to eliminate mitochondria in maturing lens fiber cells. Differentiation-state transcriptional analysis of embryonic chicken lenses was performed following microdissection of 100 embryonic day 13 (E13) chicken lenses into four distinct regions that represent a continuum of lens cell differentiation states: lens central epithelium (EC), equatorial epithelium (EQ), cortical fibers (FP), and central fibers (FC). Further analysis of the transcriptional content of biologically replicate samples was performed by Illumina directional mRNA sequencing and resulting reads mapped by TopHat and assembled with Cufflinks.
2014-07-02 | E-GEOD-53976 | biostudies-arrayexpress
Project description:Methylation at cytosines (mCG) is a well-known regulator of gene expression but its requirements for cellular differentiation have yet to be fully elucidated. A well-studied cellular differentiation model system is the eye lens, consisting of a single anterior layer of epithelial cells that migrate laterally and differentiate into a core of fiber cells. Here, we explore the genome-wide relationships between mCG methylation, chromatin accessibility and gene expression during differentiation of eye lens epithelial cells into fiber cells. Whole genome bisulfite sequencing identified 7621 genomic loci exhibiting significant differences in mCG levels between lens epithelial and fiber cells. Changes in mCG levels were inversely correlated with the differentiation state-specific expression of 1285 genes preferentially expressed in either lens fiber or lens epithelial cells (Pearson correlation r = -0.37, p < 1x10-42). mCG levels were inversely correlated with chromatin accessibility determined by Assay for transposase-accessible sequencing (ATAC-seq) (Pearson correlation r = -0.86, p < 1x10-300). Many of the genes exhibiting altered regions of DNA methylation, chromatin accessibility and gene expression levels in fiber cells relative to epithelial cells are associated with lens fiber cell structure, homeostasis and transparency. These include lens crystallins (CRYBA4, CRYBB1, CRYGN, CRYBB2), lens beaded filament proteins (BFSP1, BFSP2), transcription factors (HSF4, SOX2, HIF1A), and Notch signaling pathway members (NOTCH1, NOTCH2, HEY1, HES5). Analysis of regions exhibiting cell-type specific alterations in DNA methylation revealed an overrepresentation of consensus sequences of multiple transcription factors known to play key roles in lens cell differentiation including HIF1A, SOX2, and the MAF family of transcription factors. Collectively, these results link DNA methylation with control of chromatin accessibility and gene expression changes required for eye lens differentiation. The results also point to a role for DNA methylation in the regulation of transcription factors previously identified to be important for lens cell differentiation.
2022-03-31 | GSE196630 | GEO
Project description:Methylation at cytosines (mCG) is a well-known regulator of gene expression but its requirements for cellular differentiation have yet to be fully elucidated. A well-studied cellular differentiation model system is the eye lens, consisting of a single anterior layer of epithelial cells that migrate laterally and differentiate into a core of fiber cells. Here, we explore the genome-wide relationships between mCG methylation, chromatin accessibility and gene expression during differentiation of eye lens epithelial cells into fiber cells. Whole genome bisulfite sequencing identified 7621 genomic loci exhibiting significant differences in mCG levels between lens epithelial and fiber cells. Changes in mCG levels were inversely correlated with the differentiation state-specific expression of 1285 genes preferentially expressed in either lens fiber or lens epithelial cells (Pearson correlation r = -0.37, p < 1x10-42). mCG levels were inversely correlated with chromatin accessibility determined by Assay for transposase-accessible sequencing (ATAC-seq) (Pearson correlation r = -0.86, p < 1x10-300). Many of the genes exhibiting altered regions of DNA methylation, chromatin accessibility and gene expression levels in fiber cells relative to epithelial cells are associated with lens fiber cell structure, homeostasis and transparency. These include lens crystallins (CRYBA4, CRYBB1, CRYGN, CRYBB2), lens beaded filament proteins (BFSP1, BFSP2), transcription factors (HSF4, SOX2, HIF1A), and Notch signaling pathway members (NOTCH1, NOTCH2, HEY1, HES5). Analysis of regions exhibiting cell-type specific alterations in DNA methylation revealed an overrepresentation of consensus sequences of multiple transcription factors known to play key roles in lens cell differentiation including HIF1A, SOX2, and the MAF family of transcription factors. Collectively, these results link DNA methylation with control of chromatin accessibility and gene expression changes required for eye lens differentiation. The results also point to a role for DNA methylation in the regulation of transcription factors previously identified to be important for lens cell differentiation.
2022-03-31 | GSE196629 | GEO
Project description:FOXE3 is a lens specific transcription factor that has been associated with anterior segment ocular dysgenesis. To determine the transcriptional target(s) of FOXE3 that are indispensable for the anterior segment development, we examined the transcriptome and the proteome of cells expressing truncated FOXE3 responsible for Peters anomaly identified through linkage-coupled next-generation whole exome sequencing. We found that DNAJB1, an autophagy-associated protein, was the only candidate exhibiting differential expression in both screens. We confirmed the candidacy of DNAJB1 through chromatin immunoprecipitation and luciferase assays while knockdown of DNAJB1 in human lens epithelial cells resulted in mitotic arrest. Subsequently, we targeted dnajb1a in zebrafish through injection of a splice-blocking morpholino. The dnajb1a morphants exhibited underdeveloped cataractous lenses with persistent apoptotic nuclei. In conclusion, here we report DNAJB1 as a transcriptional target of FOXE3 in a novel pathway that is crucial for the development of the anterior segment of the eye.
2016-03-31 | PXD003436 | Pride
Project description:To explore the presence of extrachromosomal circular DNA (eccDNA) in the anterior capsule of the lens in the eyes of patients with cataract and with high myopia. Circle-Seq was performed to identify differences in the eccDNA and gene expression between the anterior capsule of the lens of patients with simple nuclear cataract (C, n = 6) and patients with nuclear cataract along with high myopia (HM, n = 6). The expression of eccDNA was confirmed using routine quantitative polymerase chain reaction. The eccDNA ranked in C and HM ranged in length from 0.017 kb – 9.9 Mb with two distinctive peaks detected at 0.2 kb and 0.5 kb, while eccDNA that were differentially expressed (up- and down-regulated) ranged in size from 0.05 kb – 57.8 kb with two distinctive peaks observed at 0.1 kb and 0.5 kb. Only 2.5 % of the eccDNA in C and 2 % in HM were > 25 kb in size. The gene-rich chromosomes contributed to more number of eccDNA/Mb, while several well-known high myopia candidate genes, including catenin delta 2 (CTNND2), ubiquitin-like with PHD and ring finger domains 1 binding protein 1 like (UHRF1BP1L) , exhibited significantly increased levels of eccDNA in the anterior capsule of the lens in patients with high myopia. This study highlighted the topologic analysis of the anterior capsule of eyes with high myopia, which is an emerging direction for research and clinical applications. These findings suggested that eccDNA was commonly detected in eyes with high myopia and cataracts, and the candidate genes for high myopia identified in previous studies were also observed in the eccDNA.
2023-04-13 | GSE207646 | GEO
Project description:Analysis of gene expression in mouse lens epithelium with or without UVB-irradiation in mouse eye lens. Results provide insight into a role for the respons to UVB-irradiation in lens epithelial cells.
2019-02-13 | GSE126294 | GEO
Project description:The purpose of this study was to investigate/characterize age- and sex-dependent changes in transcriptomic profile in a mouse model of cataract surgery that mimics human cataract surgery. This surgery involves the removal of lens fiber cells (LFC) leaving behind the lens capsule and associated lens epithelial cells (LEC). The lens capsule and associated remnant LECs were harvested either following cataract surgery (0 hour) or 24 hours later. Fiber cells were collected at the time of surgery, equivalent to 0 hour, and analyzed separately from epithelial cells. For samples from LEC, each biological replicate is a pool of 5 lens capsules from 5 independent mice. For samples from LFC, each biological replicate is a pool of 2 fiber cell masses from two independent mice. Mice were either 24 months old (Aged), or 3 months old (Young).
2021-07-10 | GSE166619 | GEO
Project description:FOXE3 is a lens specific transcription factor that has been associated with anterior segment ocular dysgenesis. To determine the transcriptional target(s) of FOXE3 that are indispensable for the anterior segment development, we examined the transcriptome and the proteome of cells expressing truncated FOXE3 responsible for Peters anomaly identified through linkage-coupled next-generation whole exome sequencing. We found that DNAJB1, an autophagy-associated protein, was the only candidate exhibiting differential expression in both screens. We confirmed the candidacy of DNAJB1 through chromatin immunoprecipitation and luciferase assays while knockdown of DNAJB1 in human lens epithelial cells resulted in mitotic arrest. Subsequently, we targeted dnajb1a in zebrafish through injection of a splice-blocking morpholino. The dnajb1a morphants exhibited underdeveloped cataractous lenses with persistent apoptotic nuclei. In conclusion, we have identified DNAJB1 as a transcriptional target of FOXE3 in a novel pathway that is crucial for development of the anterior segment of the eye.
2016-03-24 | GSE76389 | GEO