RT Journal Article
SR Electronic
T1 A Shared Transcriptional Identity for Forebrain and Dentate Gyrus Neural Stem Cells from Embryogenesis to Adulthood
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0271-21.2021
DO 10.1523/ENEURO.0271-21.2021
A1 Michael J. Borrett
A1 Nareh Tahmasian
A1 Brendan T. Innes
A1 Gary D. Bader
A1 David R. Kaplan
A1 Freda D. Miller
YR 2022
UL http://www.eneuro.org/content/early/2022/01/12/ENEURO.0271-21.2021.abstract
AB Adult neural stem cells (NSCs) reside in two distinct niches in the mammalian brain, the ventricular-subventricular zone (V-SVZ) of the forebrain lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus. They are thought to be molecularly distinct since V-SVZ NSCs produce inhibitory olfactory bulb (OB) interneurons and SGZ NSCs excitatory dentate granule neurons. Here, we have asked whether this is so by directly comparing V-SVZ and SGZ NSCs from embryogenesis to adulthood using single-cell transcriptional data. We show that the embryonic radial glial precursor (RP) parents of these two NSC populations are very similar, but differentially express a small cohort of genes involved in glutamatergic versus GABAergic neurogenesis. These different RPs then undergo a similar gradual transition to a dormant adult NSC state over the first three postnatal weeks. This dormancy state involves transcriptional shutdown of genes that maintain an active, proliferative, prodifferentiation state and induction of genes involved in sensing and regulating their niche environment. Moreover, when reactivated to generate adult-born progeny, both populations reacquire a development-like state and re-express proneurogenic genes. Thus, V-SVZ and SGZ NSCs share a common transcriptional state throughout their lifespans and transition into and out of dormancy via similar trajectories.Significance StatementThis work furthers our understanding of the molecular similarities and differences between the two major populations of adult neural stems [neural stem cell (NSC)] in the mammalian brain: ventricular-subventricular zone (V-SVZ) NSCs and subgranular zone (SGZ) NSCs. We have analyzed high throughput single-cell RNA-sequencing (scRNA-Seq) data for these two NSC populations from embryogenesis through to adulthood and show that while not identical, both populations exhibit a conserved forebrain NSC signature and are transcriptionally similar throughout their lifespans despite the different types of neurons they generate. Moreover, we show that both populations progress from active embryonic precursors to postnatal dormant NSCs along a similar timeframe, and that in both cases reactivation involves a transition back to a development-like state.