Fig. 1: Multi-omic atlas of brain organoid development reveals developmental hierarchies and critical stages of fate decision.

a, Schematic of the experimental design and UMAP embedding of integrated multi-omic metacells. Organoids from three iPS cell lines and one ES cell line were dissociated for paired scRNA-seq and scATAC-seq at time points spanning 4 days to 2 months of development. The two modalities were integrated to form metacells with RNA and ATAC components. EB, embryoid body; IPs, intermediate progenitors; N.ect., neuroectoderm; N.epi., neuroepithelium; PSCs, pluripotent stem cells. b, Examples of loci with differential accessibility during organoid development from pluripotency. c, Schematic of the branch-inference strategy. High-resolution clusters were assigned to branches on the basis of terminal fate transition probabilities calculated based on RNA velocity. d, Branch visualization in a force-directed layout. The circles represent high-resolution clusters of metacells coloured by assignment (neuroepithelium (grey); non-telencephalon progenitors (teal); telencephalon progenitors (plum); dorsal telencephalon (orange); ventral telencephalon (purple)). e, Graph representation of regional branches coloured by mean expression (log[transcript counts per 10,000 + 1]) (top) and gene activity (log[transcript counts per 10,000 + 1]) (bottom) of marker genes. The range of values is indicated for each plot. Norm., normalized. f, Stage- and branch-specific gene expression and motif enrichment z-score (Methods). Values are minimum–maximum (min–max) scaled across rows. N.t., non-telencephalon; t., telencephalon.