Identification and characterization of human retinal stem cells capable of retinal regeneration
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ABSTRACT:
PROVIDER: PRJNA1170898 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30921769_1.fastq.gz | Fastqsanger.gz | |||
| SRR30921769_2.fastq.gz | Fastqsanger.gz | |||
| SRR30921770_1.fastq.gz | Fastqsanger.gz | |||
| SRR30921770_2.fastq.gz | Fastqsanger.gz | |||
| SRR30921771_1.fastq.gz | Fastqsanger.gz |
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Project description:Human retinal stem cells hold great promise in regenerative medicine, yet their existence and characteristics remain elusive. Here, we preformed single-cell multi-omics and spatial transcriptomics of human fetal retinas and uncovered a novel cell subpopulation, human neural retinal stem-like cells (hNRSCs), distinct from RPE stem-like cell and traditional retinal progenitor cells. These hNRSCs reside in the peripheral retina within the ciliary marginal zone, exhibiting substantial self-renewal and differentiation potential. We conducted single-cell and spatial transcriptomic analysis of human retinal organoids (hROs), and revealed hROs have remarkable similar hNRSCs consistent with fetal retina, capable of regenerating all retinal cells. Furthermore, we identified crucial transcription factors, notably MECOM, governing hNRSC commitment to neural retinogenesis and regulating repair processes in hROs. Transplanting hRO-derived hNRSCs into the rd10 mouse of rapid retinal degeneration significantly repairs the degenerated retina and restores visual function. Together, our work identifies and characterizes a unique category of retinal stem cells from human retinas, underscoring their regenerative potential and promise for transplantation therapy.
2024-12-31 | GSE279113 | GEO
Project description:Human retinal stem cells (hRSCs) hold great promise in regenerative medicine due to their ability to directly differentiate into retinal cells. However, the characteristics and roles of hRSCs remain ambiguous. Here, we employed single-cell multi-omics profiles of human ciliary marginal zone (CMZ) of fetal retinas and human retinal organoids (hROs). We discovered a unique cell population of human retinal stem-like cells (hRSLCs) that specifically resides in the retinal tip and non-pigmented CMZ and possess a new regenerative lineage into neural retinal cells. Analysis of single cell and spatial transcriptomes show that the hRSLCs of hRO exhibit consistent characterization of cellular and molecular functions with fetal retinas. Functionally, several transcription factors were identified involved in the regulation of stemness from single cell RNA-seq and ATAC-seq data, and deficiency of gene MECOME in hRSLCs leds to impaired homeostasis and diminished retinal regeneration. Furthermore, transplantation of hRO-derived hRSLCs into retinal degeneration mice exhibit the high potential for retinal repair and improved visual function. Our work combines single cell multi-omics and organoid technologies to identify and comprehensively characterize a promising hRSLCs population in both human fetal retinas and organoid, opening up new avenues for potential therapy in retinal regeneration.
2024-12-31 | GSE242057 | GEO
Project description:Human retinal stem cells (hRSCs) hold great promise in regenerative medicine due to their ability to directly differentiate into retinal cells. However, the characteristics and roles of hRSCs remain ambiguous. Here, we employed single-cell multi-omics profiles of human ciliary marginal zone (CMZ) of fetal retinas and human retinal organoids (hROs). We discovered a unique cell population of human retinal stem-like cells (hRSLCs) that specifically resides in the retinal tip and non-pigmented CMZ and possess a new regenerative lineage into neural retinal cells. Analysis of single cell and spatial transcriptomes show that the hRSLCs of hRO exhibit consistent characterization of cellular and molecular functions with fetal retinas. Functionally, several transcription factors were identified involved in the regulation of stemness from single cell RNA-seq and ATAC-seq data, and deficiency of gene MECOME in hRSLCs leds to impaired homeostasis and diminished retinal regeneration. Furthermore, transplantation of hRO-derived hRSLCs into retinal degeneration mice exhibit the high potential for retinal repair and improved visual function. Our work combines single cell multi-omics and organoid technologies to identify and comprehensively characterize a promising hRSLCs population in both human fetal retinas and organoid, opening up new avenues for potential therapy in retinal regeneration.
2024-12-31 | GSE243314 | GEO
Project description:Background: Adult zebrafish spontaneously regenerate their retinas after damage. Although a number of genes and signaling pathways involved in regeneration have been identified, the extent of mechanisms regulating regeneration is unclear. Small non-coding RNAs, microRNAs (miRNAs), that regulate regeneration of various tissues in lower vertebrates were examined for their potential roles in regulating zebrafish retinal regeneration. Results: To investigate the requirement of miRNAs during zebrafish retinal regeneration, we knocked down the expression of the miRNA-processing enzyme Dicer in retinas prior to light-induced damage. Dicer loss significantly reduced proliferation of Müller glia-derived neuronal progenitor cells during regeneration. To identify individual miRNAs with roles in retina regeneration, we collected retinas at different stages of light damage and performed small RNA high-throughput sequencing. We identified subsets of miRNAs that were differentially expressed during active regeneration but returned to basal levels once regeneration was completed. To validate the roles of differentially expressed miRNAs, we knocked down 6 different miRNAs that were upregulated in expression during regeneration and demonstrated that they have distinct effects on neuronal progenitor cell proliferation and migration during retina regeneration. Conclusions: miRNAs are necessary for retinal regeneration. miRNA expression is dynamic during regeneration. miRNAs function during initiation and progression of retinal regeneration. Identification of miRNAs before, during and after completion of zebrafish retinal regeneration
2014-09-20 | E-GEOD-58702 | biostudies-arrayexpress
Project description:Identification and Characterization of Human Retinal Stem-Like Cells with Regenerative Potential
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Project description:RNA-seq to identify transcriptome of microglia and macrophages during zebrafish retinal regeneration
2019-03-18 | GSE120467 | GEO
Project description:Many genes are known to regulate Müller glia (MG)-dependent retinal regeneration following widespread tissue damage. Conversely, genes controlling regeneration following limited retinal cell loss, per degenerative disease, are undefined. Studying regeneration in the context of selective cell loss is important as evidence suggests injury specifics inform the regenerative process. Here, transgenic zebrafish enabling inducible selective retinal ganglion cell (RGC) ablation were combined with single cell multiomics and CRISPR/Cas9-based knockout methods to screen 101 genes for effects on RGC regeneration. We identified 18 regulators of RGC regeneration- seven knockouts inhibited and eleven promoted RGC regeneration. Surprisingly, 35 of 36 known/implicated regulators of retinal tissue regeneration following widespread damage were not required for RGC regeneration, and seven of these knockouts actually enhanced RGC replacement kinetics, including sox2, olig2, and ascl1a. Mechanistic analyses revealed ascl1a knockout increased the propensity of progenitor cells to produce RGCs; i.e., biased progenitor cell fate. These data demonstrate plasticity in how MG can convert to a stem-like state and context-specificity in how genes function during regeneration. Increased understanding of how disease-relevant cell types can be selectively regenerated will, support the development of disease-tailored regenerative therapeutics.
2024-05-27 | GSE268179 | GEO
Project description:Retinal ganglion cells (RGCs) and retinal pigment epithelium (RPE) cells are two retinal cell types that are affected by the most prevalent retinal diseases leading to irreversible blindness, such as glaucoma affecting the former and age-related macular degeneration affecting the latter. One of the most promising approaches for the therapy of these diseases is via the autologous transplantation of RGC or RPE cells derived from the induced pluripotent stem cells (iPSCs). This emphasizes the importance of detailed characterization and understanding of the mechanisms of differentiation of iPSCs into retinal lineages on the genome-wide scale. Such information can be used to identify novel crucial regulators of differentiation, optimisation of differentiation protocols to make them more efficient and safe, identification of novel specific biomarker signatures of differentiated cells. In this study, we performed the genome-wide transcriptome analysis of terminally differentiated RGC and RPE lineages, as well as intermediate retinal progenitor cells (RPCs) of optic vesicles (OVs) derived from the human induced pluripotent stem cells (iPSCs). In our analysis we specifically focused on the classes of transcripts that encode regulators of gene expression, such as transcription factors, epigenetic factors, and components of signaling pathways.
2017-03-22 | GSE96853 | GEO
Project description:In the retina of adult teleosts, stem cells are sustained in two specialized niches: the ciliary marginal zone (CMZ) and the microenvironment surrounding adult Müller glia. Recently, Müller glia were identified as the regenerative stem cells in the teleost retina. Secreted signaling molecules that regulate neuronal regeneration in the retina are largely unknown. In a microarray screen to discover such factors, we identified midkine-b (mdkb). Midkine is a highly conserved heparin-binding growth factor with numerous biological functions. The zebrafish genome encodes two distinct midkine genes: mdka and mdkb. Here, we describe the cellular expression of mdka and mdkb during retinal development and the initial, proliferative phase of photoreceptor regeneration. The results show that in the embryonic and larval retina mdka and mdkb are expressed in stem cells, retinal progenitors and neurons in distinct patterns that suggest different functions for the two molecules. Following the selective death of photoreceptors in the adult, mdka and mdkb are co-expressed in horizontal cells and proliferating Müller glia and their neurogenic progeny. These data reveal that Mdka and Mdkb are signaling factors present in the retinal stem cell niches in both embryonic and mature retinas, and that their cellular expression is actively modulated during retinal development and regeneration. Experiment Overall Design: As a means to identify genes necessary for photoreceptor regeneration, we evaluated transcriptional in the retina of the zebrafish as photoreceptors are regenerated. Albino zebrafish were dark adapted, then half were exposed to bright constant light and half were returned to normal lighting. After 72hrs of light exposure, retinal RNA was isolated and analysis of gene expression was performed using Affymetriz zebrafish gene arrays.
2009-01-13 | E-GEOD-13999 | biostudies-arrayexpress
Project description:Following photoreceptors ablation by intense light exposure, adult zebrafish are capable of complete regeneration due to the ability of their Müller glia (MG) to re-enter the cell cycle, creating progenitors that differentiate into new photoreceptors. The majority of previous reports on retinal regeneration focused on the first few days of the regenerative response, which include MG cell-cycle re-entry and progenitor cell proliferation. With this study, we analyzed the full 28-day time-course of regeneration by pairing a detailed morphological/immunological analysis with RNA-seq transcriptional profiling at 8 key time points during retinal regeneration. We observed several novel findings. First, we provide evidence for two separate peaks of MG gliosis, with the secondary gliotic peak occurring after MG cell-cycle re-entry. Second, we highlight a distinct transcriptional shift between 5- and 10-days post lesion that highlights the transition from progenitor proliferation to differentiation into new photoreceptors. Third, we show distinctly different patterns of transcriptional recovery of the photoreceptor opsins at 28 days post lesion. Finally, using differential gene expression analysis, we revealed that the established functional recovery of the retina at 28 days post lesion does not, in fact, return to an undamaged transcriptional state, potentially redefining what the field considers complete regeneration. Together, to our knowledge, this work represents the first histological and transcriptomic map of a 28-day time-course of retinal regeneration in adult zebrafish.
2021-10-11 | GSE180518 | GEO