Spatial organization of the mouse retina at single cell resolution

Abstract

The visual signal processing in the retina requires the precise organization of diverse neuronal types working in concert. We performed spatial transcriptomic profiling of over 100,000 cells from the mouse retia, uncovering the spatial distribution of all major retina cell types with over 100 cell subtypes. Our data revealed that the retina is organized in a laminar structure at the major cell type and subgroup level, both of which has strong correlation with the birth order of the cell. In contrast, overall random dispersion of cells within sub-laminar layers indicates that retinal mosaics are driven by dendritic field patterning rather than neuron soma placement. Through the integration of single cell transcriptomic and spatial data, we have generated the first comprehensive spatial single cell reference atlas of the mouse retina, a resource to the community and an essential step toward gaining a comprehensive understanding of the mechanism of retinal function.

Comprehensive single-cell atlas of the mouse retina

“…5b). A non-GABAergic non-glycinergic (nGnG) type 4, AC36, is split into C58 and C61 (AC36A and AC36B), consistent with previous finding of two morphologically distinct AC36 types in the INL and displaced in the GCL, stratifying to S3 and S5 sublaminae of the IPL 10,28 . By examining the list of differentially expressed genes (DEG) between the two broadly isolated types 28 , we annotated AC36A as the S3 type by the increased markers such as Gbx2, Tac1, and Pcdh8 and AC36B as the S5 type by Gad1, Gad2, and Id4.…”

“…Single cell technologies have opened a window into knowledge of cellular heterogeneity and intricate cell-to-cell interactions that cannot currently be resolved at the tissue level and have allowed exploration of individual cellular expression signatures, which can be mapped to unique molecular cell types 6,7 . The resulting cell atlas can serve as a foundation for numerous applications, including the annotation of cell types in other scRNAseq experiments 8 , the identification of differentially expressed targets for purification or manipulation 9 , and the generation of marker panels useful for single-molecule imaging, including spatial profiling 10 . While studies have demonstrated cell type heterogeneities in various tissues, several perplexing issues remain to be addressed in establishing a comprehensive cell atlas such as the agreement on cell type definitions across different experiments or whether enough cells have been profiled to exhaust all existing cell types.…”

Recent Achievements in the Heterogeneity of Mammalian and Human Retinal Pigment Epithelium: In Search of a Stem Cell

“…Using the Drop-Seq technology, a scRNA-Seq of postnatal mouse retinas was performed [19,50]. By integrating transcriptomic and single cell spatial data, the first comprehensive reference spatial atlas of single cells in the mouse retina has been created [51]. The data obtained have allowed for an interspecies comparison of human, monkey, mouse, and chicken retinas, which reveals conserved and non-conserved groups of genes [52].…”

Aptamer-based monitoring of drug uptake into cells and vertebrates

“…Recently, quantitative measurement of therapeutics in cancer models has been demonstrated using instrumentation such as MALDI-MS. 10 In all of these cases, cells and tissues must be lysed 11,12 or embedded, frozen, and cross sectioned, thus precluding real-time cellular measurements 13 and non-invasive animal studies, 14 thereby limiting studies to bulk cellular populations. 15,16 Confocal microscopy, two photon microscopy, near infrared imaging, and positron emission tomography, on the other hand, have been extremely valuable for non-invasive and real-time monitoring of biomolecules, 17 cellular processes, 18,19 and tissue patterning. 20,21 Indeed, using fluorescent dyes and probes, imaging has enabled the study of oxidative stress 22 and lipid membrane organization in whole organisms 23 , characterization of in vivo biodistribution properties of drug delivery vehicles, 24 longitudinal monitoring of inflammation in animals, 25 tracking of cellular growth and apoptosis, 26,27 and recording of brain circuitry activity.…”