Single-cell RNA-seq analysis revealed long-lasting adverse effects of tamoxifen on neurogenesis in prenatal and adult brains

Chia‐Ming Lee, Liqiang Zhou, Jiping Liu, Jiayu Shi, Yanan Geng, Min Liu, Jiaruo Wang, Xinjie Su, Nicholas Barad, Junbang Wang,

Proceedings of the National Academy of Sciences · 2020 · 51 citations · 59 references

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Abstract

Significance The tamoxifen (TAM)-inducible CreER/LoxP system is one of the most widely used genetic tools that have enabled precise gene manipulation in distinct cell subpopulations at any specific time point and labeling of any cell types for genetic fate mapping. We report that administration of TAM during early stages of cortical neurogenesis inhibits neural progenitor cell proliferation and impaired cortical neurogenesis, dendritic morphogenesis, synaptic density, and gliogenesis in postnatal offspring. By employing single-cell RNA sequencing analysis combined with in vivo and in vitro assays, we found TAM could exert these drastic effects through dysregulating the Wnt-Dmrta2 signaling pathway. This study shows that care must be taken when using the TAM-induced CreER/LoxP system for neural lineage tracing and genetic manipulation studies.

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