Modeling the Evolution of Human Brain Development Using Organoids

Abstract

In a recent issue of Nature, Kanton et al. explore human brain evolution and development by profiling the single-cell transcriptomes and epigenomes of cerebral organoids derived from human, chimpanzee, and macaque stem cells. Their results reveal key molecular characteristics that differentiate humans and non-human primates at the earliest stages of brain development.

Figure 1.. Connecting the genomic and phenotypic evolution of the human brain.

A) Left: Genetic differences between humans and chimpanzees, ranging from single nucleotide changes (SNCs) to large structural changes. Right: Phenotypic differences between humans and chimpanzees include an expanded brain, extended projections of the arcuate fasciculus involved in language, and divergent molecular features in homologous cell types. B) Kanton et al. perform single cell ATAC-seq (scATAC-seq) and single cell RNA-seq (scRNA-seq) in developing brain organoids from humans, chimpanzees and macaques. CDH7 is an example of a differentially expressed (DEX) gene with human-specific increases in both gene expression and chromatin accessibility. Single-cell RNA-seq was also performed in adult human, chimpanzee and macaque prefrontal cortex, which revealed that astrocytes have the greatest number of human-specific DEX genes, as compared to excitatory neurons, inhibitory neurons, and oligodendrocytes. HAR, human accelerated region.