Fig. 4: Multimodal integration provides a digital organoid representation of human retinal neurogenesis.
From: Multimodal spatiotemporal phenotyping of human retinal organoid development
a, Schematic for integrating accessible chromatin, transcriptome and protein modalities into spatially resolved and segmented nuclei. High-resolution clusters were generated from scSeq data (RNA/ATAC metacells) of the closest matching timepoints to the imaging data. Label transfer was predicted based on correlation of RNA and protein features in sequenced cells and imaged nuclei, respectively. Left UMAP shows timecourse metacell embedding based on transcriptome and colored by cell type with 39-week cells highlighted. Right UMAP shows nuclei embedding based on protein features colored according to label transfer from the transcriptome space. b, Overview and laminar zoom of a representative 39-week retinal organoid colored based on nuclei type assignment from the label transfer. c,d, Representative 39-week organoid nuclei colored based on RNA expression (c) or chromatin accessibility (d) of markers for PRs (CRX, c; chr17-81655189–81657223, d) or MG (HES1, c; chr11-126082119–126083088, d). e, Multimodal integration across the other timepoints. Left metacell embedding colored based on indicated timepoint. Right nuclei UMAP colored by label transfer from the transcriptome space. f, Timecourse retinal organoids colored based on VSX2 transcript expression. Boxed inset shows zoom with inner (I) to outer (O) orientation. g, Heat map shows VSX2 expression densities along the inner–outer and pseudotime axes. Dashed lines demarcate stages (vertical) and the INL (horizontal). 1, 2 and 3 refer to the organoid developmental stage as in Fig. 2e. h, Heat map showing expression of RGCs (POU4F1), MG (HES1) and PR (CRX) markers along the inner–outer and pseudotime axes. i, Heat map showing nuclei type abundance densities for the major annotated retinal organoid cell types/states along the inner–outer and pseudotime axes. j, Density plots showing proportion of each annotated nuclei type over the trajectory. Inter., intermediate; Pt, pseudotime; wk, weeks.
