Single-Cell Analysis of Human Retina Identifies Evolutionarily Conserved and Species-Specific Mechanisms Controlling Development

Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution

“…Human retinal organoids have been used to study retinal development and disease (Foltz and Clegg, 2019;Kruczek and Swaroop, 2020) but, unlike the real human retina, currently used organoids are not five-layered and have not been shown capable of rapidly transmitting light responses synaptically to inner retinal layers. Additional barriers to modeling genetic diseases of the retina are the difficulty of producing organoids in large quantities and the lack of a comprehensive quantitative comparison of gene expression between cell types in organoids and adult human retinas (Collin et al, 2019;Kim et al, 2019;Lu et al, 2020). For cell types in retinal organoids, it is therefore not well understood whether and when their gene expression matches that of the adult human retina.…”

Cluster similarity spectrum integration of single-cell genomics data

“…We applied the above six integration methods including CSS, Scanorama, MNN, Harmony, Seurat v3 and LIGER to another time course scRNA-seq data set of human retinal organoids and primary retina, where cells were annotated as 11 different cell types [22] ( Supplementary Fig. 4).…”

“…Single-cell transcriptome barcoding was performed using inDrops [3] and following the protocol by Zilionis et al, 2017 [22]. Shortly, generated single-cell suspension was co-encapsulated with RT-lysis mix and barcoded hydrogel beads (Droplet Genomics) into 3-4 nl droplets.…”

“…The scRNA-seq data set of retinal organoids and primary retina samples, including the metadata and cell type annotation, were retrieved from GEO (accession GSE138002) [22]. The retinal organoid sample cultured for 24 days was excluded from the analysis as it only contains 24 cells.…”

Human Developmental Cell Atlas: milestones achieved and the roadmap ahead

“…Organ atlases of lung, heart, gastrointestinal tract, kidney, germ cells and gonads, and brain (Table 1) underscore the importance of studying human samples and reveal the unique aspects of human development not conserved with animal model systems [64][65][66] . These include timelines of development during gestation, cell type markers and expression pattern of transcription factors between mouse and human organs 67,68 Early developmental studies of the brain have focused on human and primate cortical development [73][74][75][76][77][78][79][80][81][82] . The developing human and rodent midbrain, which contains the clinically relevant dopaminergic cell groups that are lost in Parkinson's disease, has also been extensively studied 68,83,84 , as has the developing mouse spinal cord and cerebellum 85,86 , the hypothalamic arcuate nucleus and the diencephalon 87 .…”