Age-related histone loss and altered histone acetylation in mouse retinal pigment epithelium. [Total RNA]
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ABSTRACT:
PROVIDER: PRJNA989279 | ENA |
REPOSITORIES: ENA
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Project description:Histones are pivotal carriers of epigenetic information through post-translational modifications (PTMs), crucial for regulating gene expression, proper cellular function and maintaining cell identity. Perturbations in histone levels within the aging genome can profoundly impact chromatin structure and gene expression profiles. In this study, we examined the effects of age-related changes on histone levels and histone acetylation in the retinal pigment epithelium (RPE) and retina of mice. Our findings revealed a global reduction in histones H1, H2A, H2B, H3, and H4 within the aged RPE/choroid, while the neural retina remained unaffected. Transcriptome analysis unveiled a significant downregulation of histone genes in the aged RPE/choroid, including key components of the histone locus body (HLB) complex involved in histone pre-mRNA processing. Knockdown of HINFP, a critical HLB component, in human RPE cells resulted in histone loss, induction of senescence, and upregulation of senescence-associated secretory phenotype (SASP) markers. Replicative aging of human RPE cells exhibited progressive histone loss and acquisition of the SASP phenotype. Immunostaining of human retina sections demonstrated a gradual decline in histones within the aging RPE. Additionally, aging in mice RPE/choroid led to diminished global histone acetylation levels, particularly H3K14ac, H3K56ac, and H4K16ac marks. These alterations in histone acetylation were metabolically driven and correlated with changes in acetyl-CoA abundance. Collectively, our findings highlight the characteristic loss of histones as a hallmark of aging in the RPE/choroid, shedding light on potential mechanisms linking histone dynamics, cellular senescence, and age-related functional changes in RPE cells.
2023-07-15 | GSE236220 | GEO
Project description:Age-related histone loss and altered histone acetylation in mouse retinal pigment epithelium.
| PRJNA989276 | ENA
Project description:Histones are pivotal carriers of epigenetic information through post-translational modifications (PTMs), crucial for regulating gene expression, proper cellular function and maintaining cell identity. Perturbations in histone levels within the aging genome can profoundly impact chromatin structure and gene expression profiles. In this study, we examined the effects of age-related changes on histone levels and histone acetylation in the retinal pigment epithelium (RPE) and retina of mice. Our findings revealed a global reduction in histones H1, H2A, H2B, H3, and H4 within the aged RPE/choroid, while the neural retina remained unaffected. Transcriptome analysis unveiled a significant downregulation of histone genes in the aged RPE/choroid, including key components of the histone locus body (HLB) complex involved in histone pre-mRNA processing. Knockdown of HINFP, a critical HLB component, in human RPE cells resulted in histone loss, induction of senescence, and upregulation of senescence-associated secretory phenotype (SASP) markers. Replicative aging of human RPE cells exhibited progressive histone loss and acquisition of the SASP phenotype. Immunostaining of human retina sections demonstrated a gradual decline in histones within the aging RPE. Additionally, aging in mice RPE/choroid led to diminished global histone acetylation levels, particularly H3K14ac, H3K56ac, and H4K16ac marks. These alterations in histone acetylation were metabolically driven and correlated with changes in acetyl-CoA abundance. Collectively, our findings highlight the characteristic loss of histones as a hallmark of aging in the RPE/choroid, shedding light on potential mechanisms linking histone dynamics, cellular senescence, and age-related functional changes in RPE cells.
2023-07-15 | GSE236219 | GEO
Project description:Age-related histone loss and altered histone acetylation in mouse retinal pigment epithelium. [polyA RNA]
| PRJNA989278 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-07-15 | GSE236221 | GEO
Project description:Retinal pigment epithelial cells are critical for eye function and loss of cell function is linked to age-related blindness. Relatively little is known about the transcriptional regulatory networks in these cells. The datasets presented here are ChIP-seq experiments for RNA polymerase II , transcription factors and histone modifications in human retinal pigment epithelial cells. ChIP-Seq for transcription factors, RNA polymerase, histone modifications and CTCF in retinal pigment epithelial cells
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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: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.
2015-09-23 | E-GEOD-64264 | biostudies-arrayexpress
Project description:Retinal pigment epithelial cells are critical for eye function and loss of cell function is linked to age-related blindness. Relatively little is known about the transcriptional regulatory networks in these cells. The datasets presented here are ChIP-seq experiments for RNA polymerase II , transcription factors and histone modifications in human retinal pigment epithelial cells.
2014-08-03 | GSE60024 | GEO
Project description:The microarray technique was used to investigate gene expression level changes in human retinal pigment epithelium (RPE) microdissected from fetal eyes (13 and 16 weeks of gestation) and adult eyes (40-60 years old). The gene expression analysis of human fetal RPE during development were performed and compared to human native RPE. Of the 45,033 probe sets on the microarray, 30,736 were detected. 3498 differentially expressed genes could be clustered into 8 patterns of expression that were statistically significant. Analyzing expression pattern of genes coding for key functions (pigment synthesis, visual cycle, phagocytosis, adherens and tight junction, transcellular transport) indicates human RPE achieved a high degree of maturity at early pregnancy. Compare to 154 signature genes of RPE, 148 candidate genes were identified in this studies including 53 down-regulated genes and 5 up-regulated genes. qRT2-PCR results showed similar expression trends with the microarray at three time points.These findings indicate human RPE has different expression pattern compared to other animals. A three chip study using total RNA pooled equally from three 13-week fetal eyes, two 16-week fetal eyes and two adult eyes for three time points (13, 16 week gestation and mature adult eye). Experiment was repeated in another group samples. This is a six chip study totally.
2013-01-01 | E-GEOD-40980 | biostudies-arrayexpress