Journal
DEVELOPMENT
Volume 149, Issue 5, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.200028
Keywords
Neural stem cell; Adult neurogenesis; Regional identity; Olfactory bulb; Development
Categories
Funding
- National Institutes of Health [2R01NS069893]
- Ohio Eminent Scholar Fund from the State of Ohio
- Chan Zuckerberg Initiative grant [2017-173968]
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The basic helix-loop-helix transcription factor Olig2 defines a unique subset of adult neural stem cells in the ventral aspect of the subventricular zone, playing an important role in cell cycle, metabolic properties, and specification of olfactory bulb interneuron subtypes.
Distinct neural stem cells (NSCs) reside in different regions of the subventricular zone (SVZ) and generate multiple olfactory bulb (OB) intemeuron subtypes in the adult brain. However, the molecular mechanisms underlying such NSC heterogeneity remain largely unknown. Here, we show that the basic helix-loop-helix transcription factor Olig2 defines a subset of NSCs in the early postnatal and adult SVZ. Olig2-expressing NSCs exist broadly but are most enriched in the ventral SVZ along the dorsoventral axis complementary to dorsally enriched Gsx2-expressing NSCs. Comparisons of Olig2-expressing NSCs from early embryonic to adult stages using single cell transcriptomics reveal stepwise developmental changes in their cell cycle and metabolic properties. Genetic studies further show that cross-repression contributes to the mutually exclusive expression of Olig2 and Gsx2 in NSCs/progenitors during embryogenesis, but that their expression is regulated independently from each other in adult NSCs. Finally, lineage-tracing and conditional inactivation studies demonstrate that Olig2 plays an important role in the specification of OB intemeuron subtypes. Altogether, our study demonstrates that Olig2 defines a unique subset of adult NSCs enriched in the ventral aspect of the adult SVZ.
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