In Nature this week, researchers report a genetic analysis of developing human and great ape cerebral organoids that reveals aspects of brain development unique to humans. Using single-cell transcriptomics and other approaches, Max Planck Institute researchers and their colleagues analyzed stem cell-derived human cerebral organoids over the course of their development, then compared the results with how chimpanzee and macaque cerebral organoids develop. Among their findings is a slower pace of human neuronal development relative to the two animals, as well as a divergence in chromatin accessibility during cortex development between humans and chimpanzees that correlated with human-specific gene expression and genetic change. "Our data provide a temporal cell atlas of great ape forebrain development and illuminate dynamic gene-regulatory features that are unique to humans," the authors write.
A method for sequencing the transcriptome and chromatin accessibility in the same cell is presented in Nature Biotechnology this week. With the technique — called droplet-based single-nucleus chromatin accessibility and mRNA expression sequencing, or SNARE-seq — accessible sites are captured by Tn5 transposase in permeabilized nuclei to permit, within many droplets in parallel, DNA barcode tagging together with the mRNA molecules from the same cells, the authors write. They use SNARE-seq to generate joint profiles of 5,081 and 10,309 cells from neonatal and adult mouse cerebral cortices, respectively. With these data, they reconstruct the transcriptome and epigenetic landscapes of major and rare cell types, uncover lineage-specific accessible sites, and connect the dynamics of promoter accessibility with transcription level during neurogenesis.