Similar Datasets
Project description:Cis-regulatory elements (CREs) play a critical role in the development, maintenance, and disease-states of all human cell types. In the human retina, CREs have been implicated in a variety of inherited retinal disorders. To characterize cell-class-specific CREs in the human retina and elucidate their potential functions in development and disease, we performed single-nucleus (sn)ATAC-seq and snRNA-seq on the developing and adult human retina and on human retinal organoids. These analyses allowed us to identify cell-class-specific CREs, enriched transcription factor binding motifs, putative target genes, and to examine how these features change over development. By comparing DNA accessibility between the human retina and retinal organoids we found that CREs in organoids are highly correlated at the single-cell level, validating the use of organoids as a model for studying disease-associated CREs. As a proof of concept, we studied the function of a disease-associated CRE at 5q14.3 in organoids, identifying its principal target gene as the miR-9-2 primary transcript and demonstrating a dual role for this CRE in regulating neurogenesis and gene regulatory programs in mature glia. This study provides a rich resource for characterizing cell-class-specific CREs in the human retina and showcases retinal organoids as a model in which to study the function of retinal CREs that influence retinal development and disease.
2021-11-16 | GSE183684 | GEO
Project description:Clinical and genetic heterogeneity associated with retinal diseases makes stem cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 150. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared to peripheral retina. Human and mouse retinal transcriptomes show remarkable similarity in developmental stages, though morphogenesis was greatly expanded in humans. Integration of DNA accessibility data allowed us to reconstruct transcriptional networks controlling photoreceptor differentiation. Our studies provide insights into human retinal development and serve as resource for molecular staging of human stem cell-derived retinal organoids.
2017-12-07 | GSE104827 | GEO
Project description:To study the development of human retina, we used single cell RNAseq at key fetal stages and followed the development of the major cell types, as well as populations of transitional cells. We also analyzed stem cell (hPSC)-derived retinal organoids; although organoids have a very similar cellular composition at equivalent ages to the fetal retina, there are some differences in gene expression of particular cell types. Moreover, the inner retinal lamination is disrupted in more advanced stages of organoids when compared with fetal retina. To determine whether the disorganization in the inner retina was due to the culture conditions, we analyzed retinal development in fetal retina maintained under similar conditions. These retinospheres develop for at least 6 months, displaying better inner retinal lamination than retinal organoids. Our scRNAseq comparisons between fetal retina, retinal organoids and retinospheres provide a new resource for developing better in vitro models for retinal disease.
2020-01-10 | GSE142526 | GEO
Project description:Retina is the fundamental unit of central nervous system, whose development is orchestrated by the intricate crosstalk of diverse RNA species. However, the molecular complexity of neural retina development remains poorly elucidated, limiting the therapy of retinal neurodegenerative diseases. Herein, we performed whole transcriptome sequencing of mouse retina in E14.5, P1, P7, P12, P17 and adult. The circRNA, lncRNA, miRNA and mRNA expression profiles of the developing retina were comprehensively characterized and the differentially expressed RNAs were screened.
2021-06-18 | GSE168093 | GEO
Project description:Single cell genomic analyses provide a new perspective on the development of complex tissues, like the vertebrate neural retina. We previously used single cell transcriptomic analysis to characterize human fetal retinal development and assessed the degree to which retinal organoids recapitulate normal fetal development. In this study we extend the transcriptomic analyses of fetal human retina to incorporate single nuclear scATAC-seq, a powerful new method to characterize potential gene regulatory networks through the changes in accessible chromatin that accompany cell state changes. The combination of scATAC-seq and sc-RNA-seq can be used to study the process of neurogenesis in the developing fetal human retina at unprecedented resolution. We identify the key transcription factors relevant to specific fates and the order of the transcription factor cascades that define each of the major retinal cell types. These transcriptomic and epigenomic features are largely recapitulated in retinal organoids; however, there are differences in Notch signaling and amacrine cell gene regulation, which are not as robust in organoids. The datasets we generated constitute an excellent resource for the continued improvement of retinal organoid technology, and have the potential to inform and accelerate regenerative medicine approaches to retinal disease.
2021-12-30 | GSE184386 | GEO
Project description:scRNA-seq of the developing human retina
| PRJNA574132 | ENA
Project description:This study provides analysis of developing mouse retina organoids derived from induced pluripotent stem cells . RNA-seq profiling was performed on 10 time points during retinal organoid development. Alignment, transcript and gene quantitation, and normalization was performed.
2017-12-07 | GSE102794 | GEO
Project description:The chicken embryo (Gallus gallus) is a classic model system for studying developmental biology. During chick development, embryonic day 8 (E8) retina are packed with multipotent neuronal precursors on the cusp of differentiation into all retinal cell types. By E18 the retina is nearly fully mature with all major retinal cell types differentiated and expressing cell type-specific genes. Whole retina were harvested from embryonic day 8 (E8), E16, and E18 developing chicken embryos. Whole cornea were also collected from E18 embryos as a reference tissue. Duplicates were obtained for each time point and total RNA was extracted from samples using a Qiagen AllPrep Mini Kit. To characterize differential gene expression in these tissues, Illumina stranded TrueSeq RNA-Seq libraries were prepared from total RNA and 125 PE sequencing reads were obtained. These data will be used to characterize retina-specific patters of gene expression as well as global changes in gene expression between critical developmental time points in the chicken retina.
2016-08-18 | GSE65938 | GEO
Project description:This experiment analyzes the mirnome of 16 retina samples and 2 Retinal Pigment Epithelium (RPE)/choroid from non-visually impaired post-mortem donors, by using smallRNAseq on a Illumina platform. The aim was to establish the catalogue of normal retina-expressed miRNAs, determine their relative abundance, and identify miRNA variants (isomiRs).
2016-01-27 | E-MTAB-3792 | biostudies-arrayexpress
Project description:To comprehensively profile cell types in the human retina, we performed single cell RNA-sequencing on 20,009 cells obtained post-mortem from three donors and compiled a reference transcriptome atlas. Using unsupervised clustering analysis, we identified 18 transcriptionally distinct clusters representing all known retinal cells: rod photoreceptors, cone photoreceptors, Müller glia cells, bipolar cells, amacrine cells, retinal ganglion cells, horizontal cells, retinal astrocytes and microglia.
2019-08-21 | E-MTAB-7316 | biostudies-arrayexpress