Single-Cell Profiling Shows Murine Forebrain Neural Stem Cells Reacquire a Developmental State when Activated for Adult Neurogenesis

单细胞分析显示小鼠前脑神经干细胞在被激活进行成人神经发生时重新获得发育状态

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作者:Michael J Borrett, Brendan T Innes, Danielle Jeong, Nareh Tahmasian, Mekayla A Storer, Gary D Bader, David R Kaplan, Freda D Miller

Abstract

The transitions from developing to adult quiescent and activated neural stem cells (NSCs) are not well understood. Here, we use single-cell transcriptional profiling and lineage tracing to characterize these transitions in the murine forebrain. We show that the two forebrain NSC parental populations, embryonic cortex and ganglionic eminence radial precursors (RPs), are highly similar even though they make glutamatergic versus gabaergic neurons. Both RP populations progress linearly to transition from a highly active embryonic to a dormant adult stem cell state that still shares many similarities with embryonic RPs. When adult NSCs of either embryonic origin become reactivated to make gabaergic neurons, they acquire a developing ganglionic eminence RP-like identity. Thus, transitions from embryonic RPs to adult NSCs and back to neuronal progenitors do not involve fundamental changes in cell identity, but rather reflect conversions between activated and dormant NSC states that may be determined by the niche environment.

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