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A unified single cell atlas of the mouse retina

ABSTRACT: Single cell RNA sequencing (scRNA-seq) has advanced the assessment of cellular heterogeneity at the single-cell resolution by identifying transcriptional similarities and differences. Data resources of scRNA-seq have been largely produced and extensively studied for the mouse retina. They serve as a powerful tool to study cellular components, transcriptome relationships, and regulatory mechanisms underlying various retinal diseases and biological processes. The large volume of mouse retinal scRNA-seq data has been released in separate repositories, limiting their widespread use in mouse retina communities. In this work, we are presenting a unified single-cell atlas for adult wild-type mouse retina using our in-house generated single-cell RNA-seq data complementing public datasets. The collected data account for over 323,000 single cells. After data integration, cell clustering, and cell type annotation, we have annotated 11 major classes and over 120 retinal cell types to form a unified single-cell reference for the mouse retina. To facilitate the public use of the reference, we have deposited it on CELLxGENE, UCSC Cell Browser, and Single Cell Portal for visualization and gene expression exploration. The unified atlas is also released to annotate new mouse retinal cells using scArches utilities. This unified reference serves an easy-to-use data resource of mouse retina communities.

ORGANISM(S): Mus musculus

PROVIDER: GSE243413 | GEO | 2024/02/15

REPOSITORIES: GEO

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Project description:This SuperSeries is composed of the SubSeries listed below. As the light sensing part of the visual system, the human retina is composed of five classes of neuron, including photoreceptors, horizontal cells, amacrine, bipolar, and retinal ganglion cells. Each class of neuron can be further classified into subgroups with the abundance varying three orders of magnitude. Therefore, to capture all cell types in the retina and generate a complete single cell reference atlas, it is essential to scale up from currently published single cell profiling studies to improve the sensitivity. In addition, to gain a better understanding of gene regulation at single cell level, it is important to include sufficient scATAC-seq data in the reference. To fill the gap, we performed snRNA-seq and snATAC-seq for the retina from healthy donors. To further increase the size of the dataset, we then collected and incorporated publicly available datasets. All data underwent a unified preprocessing pipeline and data integration. Multiple integration methods were benchmarked by scIB, and scVI was chosen. To harness the power of multiomics, snATAC-seq datasets were also preprocessed, and scGlue was used to generate co-embeddings between snRNA-seq and snATAC-seq cells. To facilitate the public use of references, we employ CELLxGENE and UCSC Cell Browser for visualization. By combining previously published and newly generated datasets, a single cell atlas of the human retina that is composed of 2.5 million single cells from 48 donors has been generated. As a result, over 90 distinct cell types are identified based on the transcriptomics profile with the rarest cell type accounting for about 0.01% of the cell population. In addition, open chromatin profiling has been generated for over 400K nuclei via single nuclei ATAC-seq, allowing systematic characterization of cis-regulatory elements for individual cell type. Integrative analysis reveals intriguing differences in the transcriptome, chromatin landscape, and gene regulatory network among cell class, subgroup, and type. In addition, changes in cell proportion, gene expression and chromatin openness have been observed between different gender and over age. Accessible through interactive browsers, this study represents the most comprehensive reference cell atlas of the human retina to date. As part of the human cell atlas project, this resource lays the foundation for further research in understanding retina biology and diseases.

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A unified single cell atlas of the mouse retina

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