Single cell RNAseq analysis revealed long-lasting adverse effects of prenatal tamoxifen administration on neurogenesis

We report that administration of tamoxifen (TAM) during early stages of cortical neurogenesis promoted precocious neural differentiation, while it inhibited neural progenitor cell (NPC) proliferation. The TAM-induced inhibition of NPC proliferation led to deficits in cortical neurogenesis, dendritic morphogenesis, synaptic formation, and cortical patterning in neonatal and postnatal offspring. Mechanistically, by employing single cell RNA sequencing (scRNA-seq) analysis combined with in vivo and in vitro assays, we showed TAM could exert these drastic effects mainly through dysregulating Wnt-Dmrta2 signaling pathway. Single cell mRNA profiles of embryonic day 12 (E12) control and tamoxifen treated C57BL/6 mouse forebrains