FIGURE 1.

Genetic and epigenetic regulation in the brain organoids. Top, genetics in brain organoids. iPSCs carrying ASD or SCZ pathogenic genes are derived from patients or gene editing. The mutation of ASD or SCZ are referring to the commonly mutated genes in GWAS databases, which are shown in middle. The ASD organoids showed macrocephaly, microcephaly phenotypes, and over-produced GABAergic neurons. The SCZ-organoids characterized abnormal proliferation of progenitor, reduced mature neurons, and disruption of synaptic function. Bottom, epigenetics in brain organoids. Combined with single-cell sequencing, ATACseq and CHIP-seq analyze epigenetics during brain organoids and human brain development, including DNA methylation, histone variants, non-coding RNA, and chromatin accessibility. Epigenetics can regulate timing during development. Epigenetic regulation is deeply influenced by environmental factors. Exposure to toxic substances, viruses, alcohol, and stress may have epigenetic effects on fetal brain development. Brain organoids infected with Zika virus during early development showed epigenetic abnormalities, impaired progenitor proliferation as well as a distinct microcephaly phenotype.