Single-cell RNA sequencing of the retina in a model of retinitis pigmentosa reveals early responses to degeneration in rods and cones
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE183206 | GEO | 2022/04/13
REPOSITORIES: GEO
Similar Datasets
Project description:Both rod and cone photoreceptors are critical for mammalian vision yet they have important functional differences. In this study, we investigate patterns of DNA methylation and chromatin accessibility in mouse rods and cones. Unexpectedly, we find that a substantial fraction of hypo-methylated regions in the rod methylome are in inaccessible chromatin. These regions show marks of active regulatory regions earlier in neuronal development and could remain undermethylated in adult rods due to their highly compact chromatin. We further identify rod- and cone-enriched regions of accessible chromatin that correspond with cell type-specificity of nearby photoreceptor gene expression. We predict novel DNA signatures of rod and cone specificity and show that NR2E3 function is necessary for rods to gain their complete ensemble of epigenomic features. Taken together, our data capture the epigenomic landscapes of retinal rods and cones, including differences relevant to chromatin structure and photoreceptor biology.
2016-03-07 | GSE72550 | GEO
Project description:Retinitis pigmentosa (RP) is a photoreceptor disease that affects approximately 100,000 people in the United States. There are currently very limited treatment options and the prognosis for most patients is progressive vision loss. Unfortunately, the understanding of the molecular underpinnings of RP initiation and progression is still poorly understood. However, the development of animal models of RP, coupled with high-throughput sequencing, has provided an opportunity to study the underlying cellular and molecular changes of this disease. Using RNA-Seq, we present the first retinal transcriptome analysis of the rd10 murine model of retinal degeneration. RNA-Seq on whole-retina samples from rd10, wild-type and GFP-expressing mouse retina. Three biological replicates of each.
2014-10-26 | E-GEOD-56473 | biostudies-arrayexpress
Project description:Cone photoreceptors are the primary initiator of visual transduction in the human retina. Dysfunction or death of rod photoreceptors precedes cone loss in many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for cone survival. Rod differentiation and homeostasis are dependent on the basic motif leucine zipper transcription factor NRL. The loss of Nrl in mice (Nrl-/-) results in a retina with predominantly S-opsin containing cones that exhibit molecular and functional characteristics of WT cones. Here we report that Nrl-/- retina undergoes a rapid but transient period of degeneration in early adulthood, with cone apoptosis, retinal detachment, alterations in retinal vessel structure, and activation and translocation of retinal microglia. However, cone degeneration stabilizes by four months of age, resulting in a thinned but intact outer nuclear layer with residual cones expressing S- and M-opsins and a preserved photopic ERG. At this stage, microglia translocate back to the inner retina and reacquire a quiescent morphology. Gene profiling analysis during the period of transient degeneration reveals misregulation of stress response and inflammation genes, implying their involvement in cone death. The Nrl-/- retina illustrates the long-term viability of cones in the absence of rods and may serve as a model for elucidating mechanisms of cone homeostasis and degeneration that would be relevant to understanding diseases of the cone-dominant human macula. Targets were generated from a pair of retinas (one Nrl-/- mouse) per biological replicate. Four biological replicates were generated for each of the five aging timepoints (1, 2, 4, 6, and 10 months post natal).
2011-11-15 | E-GEOD-33674 | biostudies-arrayexpress
Project description:Cone photoreceptors are the primary initiator of visual transduction in the human retina. Dysfunction or death of rod photoreceptors precedes cone loss in many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for cone survival. Rod differentiation and homeostasis are dependent on the basic motif leucine zipper transcription factor NRL. The loss of Nrl in mice (Nrl-/-) results in a retina with predominantly S-opsin containing cones that exhibit molecular and functional characteristics of WT cones. Here we report that Nrl-/- retina undergoes a rapid but transient period of degeneration in early adulthood, with cone apoptosis, retinal detachment, alterations in retinal vessel structure, and activation and translocation of retinal microglia. However, cone degeneration stabilizes by four months of age, resulting in a thinned but intact outer nuclear layer with residual cones expressing S- and M-opsins and a preserved photopic ERG. At this stage, microglia translocate back to the inner retina and reacquire a quiescent morphology. Gene profiling analysis during the period of transient degeneration reveals misregulation of stress response and inflammation genes, implying their involvement in cone death. The Nrl-/- retina illustrates the long-term viability of cones in the absence of rods and may serve as a model for elucidating mechanisms of cone homeostasis and degeneration that would be relevant to understanding diseases of the cone-dominant human macula.
2011-11-15 | GSE33674 | GEO
Project description:Retinitis Pigmentosa (RP) is a progressive retinal degeneration in which the retina loses nearly all of its photoreceptor cells and undergoes major structural changes. Little is known regarding the role the resident glia, the MM-CM-<ller glia, play in the progression of the disease. Here we define gene expression changes in MM-CM-<ller glial cells (MGCs) from two different mouse models of RP, the retinal degeneration 1 (rd1) and rhodopsin knock-out (Rhod-ko) models. The RNA repertoire of 28 single MGCs was comprehensively profiled, and a comparison was made between MGC from wild type (WT) and mutant retinas. Two time points were chosen for analysis, one at the peak of rod photoreceptor death and one during the period of cone photoreceptor death. MGCs have been shown to respond to retinal degeneration by undergoing gliosis, a process marked by the upregulation of GFAP. In this data, many additional transcripts were found to change. These can be placed into functional clusters, such as retinal remodeling, stress response, and immune related response. It is noteworthy that a high degree of heterogeneity among the individual cells was observed, possibly due to their different spatial proximities to dying cells, and/or inherent heterogeneity among MGCs. Retinas were dissociated and single Muller Glial Cells were picked under a dissecting microscope using a micropipette based on their distinct morphological shape. Single cell cDNAs were generated and genome wide profiles were obtained by hybridization to Affymetrix 430 2.0 microarrays. Data was normalized using MAS5.0 software. A total of 28 Muller Glial Cells were analyzed and confirmed post hoc by expression of known marker genes.
2014-10-31 | E-GEOD-35386 | biostudies-arrayexpress
Project description:Retinitis Pigmentosa (RP) is a progressive retinal degeneration in which the retina loses nearly all of its photoreceptor cells and undergoes major structural changes. Little is known regarding the role the resident glia, the Müller glia, play in the progression of the disease. Here we define gene expression changes in Müller glial cells (MGCs) from two different mouse models of RP, the retinal degeneration 1 (rd1) and rhodopsin knock-out (Rhod-ko) models. The RNA repertoire of 28 single MGCs was comprehensively profiled, and a comparison was made between MGC from wild type (WT) and mutant retinas. Two time points were chosen for analysis, one at the peak of rod photoreceptor death and one during the period of cone photoreceptor death. MGCs have been shown to respond to retinal degeneration by undergoing gliosis, a process marked by the upregulation of GFAP. In this data, many additional transcripts were found to change. These can be placed into functional clusters, such as retinal remodeling, stress response, and immune related response. It is noteworthy that a high degree of heterogeneity among the individual cells was observed, possibly due to their different spatial proximities to dying cells, and/or inherent heterogeneity among MGCs.
2014-10-31 | GSE35386 | GEO
Project description:Rod-derived Cone Viability Factor (RdCVF, alias nxnl1) is a retina-specific protein identified for its therapeutic potential in supporting cone survival during retinal degeneration. A nxnl1 knockout mouse model was created and the transcriptome used to demonstrate that the retina is compromised by the absence of nxnl1. Experiment Overall Design: In total 9 samples were analyzed, they represent three different genotypes (wt/wt, ko/wt, ko/ko) that were tested in triplicate each.
2010-02-17 | E-GEOD-13869 | biostudies-arrayexpress
Project description:Rod-derived Cone Viability Factor (RdCVF, alias nxnl1) is a retina-specific protein identified for its therapeutic potential in supporting cone survival during retinal degeneration. A nxnl1 knockout mouse model was created and the transcriptome used to demonstrate that the retina is compromised by the absence of nxnl1. Keywords: genetic modification, transcription-profile, retina
2010-01-24 | GSE13869 | GEO
Project description:The rd10 mouse is a model of retinitis pigmentosa characterized by the dysfunction of a rod-photoreceptor-specific phosphodiesterase. Compared to the rd1 mouse, retinal degeneration in the rd10 mouse begins later in age with a milder phenotype, making it ideal for investigating cell death and neuroprotective mechanisms. Alterations in the rd10 retina proteome at pre-, peak-, and post-degenerative time points were examined using a modified high-recovery filter-aided sample preparation (FASP) method and label-free mass spectrometry, generating a unique proteomic dataset on almost 3000 proteins. Our data confirmed a period of protein expression similar to age-matched wild-type mice pre-degeneration, with decreases in proteins associated with phototransduction and increases in signaling proteins at peak- and post-degenerative stages. 123 proteins were differentially expressed the rd10 retinae during peak-degeneration compared to wild-type mice. Network analysis separated these proteins into a cluster of downregulated photoreceptor proteins, and one of upregulated signaling proteins centered around GFAP, STAT3, and STAT1. This is the first study to identify alterations in STAT1 in the rd10 mouse, which were confirmed with gene expression and immunoblotting experiments. This finding proves the efficacy of our approach, and that this dataset could serve as an information source for protein alterations in retinal degeneration.
2016-03-21 | PXD002584 | Pride
Project description:Differentiation of distinct neurons in the developing retina is controlled by combinatorial action of a small subset of transcription factors and signalling molecules. Protein inhibitor of activated STAT3 (PIAS3) has been implicated in guiding the specification of both rod and cone photoreceptors through posttranslational modification of key retinal transcription factors. To investigate its role during retinal development, we deleted exon 2-5 of the mouse Pias3 gene, which resulted in complete loss of the PIAS3 protein. Pias3-/- mice did not exhibit any overt phenotype, and retinal lamination appeared normal by histology even at 18 months. We detected reduced photopic b-wave amplitude by electroretinography (ERG) analysis following green light stimulation of Pias3-/- retina at postnatal day (P) 21, suggesting a compromised visual response of medium wavelength (M) cones. No change was evident in response of short wavelength (S) cones or rod photoreceptors until 7 months. Immunohistochemistry demonstrated altered distribution of cone photoreceptors as revealed by increased S-opsin expression in the M-cone dominant dorsal retina. Transcriptome profiling of P21 and 18-month old Pias3-/- retina revealed aberrant expression of genes associated with photoreceptor function. Our studies suggest redundancy in SUMOylation-associated transcriptional control mechanisms and identify a specific though limited role of PIAS3 in modulating spatial patterning and optimal function of cone photoreceptor subtypes in the mouse retina.
2017-05-29 | GSE94011 | GEO