Single-nucleus chromatin accessibility and RNA-seq reveal impaired brain development in prenatal e-cigarette exposed neonatal rats

We studied the influence of maternal vaping on rat neonates' brain development, using single nucleus -ATAC-seq (snATAC-seq) and -RNA-seq (snRNA-seq) technologies. We found that maternal vaping distorted neuronal lineage differentiation by promoting excitatory neuron and inhibiting lateral ganglionic eminence derived inhibitory neuron differentiation. Maternal vaping also diminished microglia population in rat developing brain. Functional enrichment revealed that the distorted neuronal differentiation and reduced microglia population were associated with disrupted brain calcium homeostasis and signaling. Our findings raise the concern that maternal vaping may cause adverse long-term brain damage to the offsprings. In addition, we proposed a set of brain cell specific chromatin accessibility markers for identifying rat brain cells directly from snATAC-seq data. Pregnant rats were exposed to e-cigarette vapor during E4 to E20. Droplet based snATAC-seq and snRNA-seq were performed to study the influence of maternal vaping on neonates' brain development.