PT  - JOURNAL ARTICLE
AU  - Chia-Ming Lee
AU  - Liqiang Zhou
AU  - Jiping Liu
AU  - Jiayu Shi
AU  - Yanan Geng
AU  - Jiaruo Wang
AU  - Xinjie Su
AU  - Nicholas Barad
AU  - Junbang Wang
AU  - Yi E. Sun
AU  - Quan Lin
TI  - Single cell transcriptomic analysis revealed long-lasting adverse effects of prenatal tamoxifen administration on neurogenesis in prenatal and adult brains
AID  - 10.1101/811893
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 811893
4099  - http://biorxiv.org/content/early/2019/11/02/811893.short
4100  - http://biorxiv.org/content/early/2019/11/02/811893.full
AB  - CreER/LoxP system has enabled precise gene manipulation in distinct cell subpopulations at any specific time point upon tamoxifen (TAM) administration. This system is widely accepted to track neural lineages and study gene functions. We have observed prenatal TAM treatment caused high rate of delayed delivery and mortality of pups. These substances could promote undesired results, leading to data misinterpretation. Here, we report that TAM administration during early stages of cortical neurogenesis promoted precocious neural differentiation, while inhibited neural progenitor cell (NPC) proliferation. The TAM-induced inhibition of NPC proliferation led to deficits in cortical neurogenesis, dendritic morphogenesis, and cortical patterning in neonatal and postnatal offspring. Mechanistically, single cell RNA sequencing (scRNA-seq) analysis combined with in vivo and in vitro assays showed TAM could exert these drastic effects mainly through dysregulating the expression of Dmrta2 and Wnt8b. In adult mice, administration of TAM significantly attenuated NPC proliferation in both the subventricular zone and the dentate gyrus. This study revealed the cellular and molecular mechanisms for the adverse effects of prenatal tamoxifen administration on corticogenesis, suggesting that tamoxifen-induced CreER-LoxP system may not be suitable for neural lineage tracing and genetic manipulation studies in both embryonic and adult brains.