Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis
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Cellular diversity of the brain is largely attributed to the spatial and temporal heterogeneity of progenitor cells. In mammalian cerebral development,it has been difficult to determine how heterogeneous the neural progenitor cells are, owing to dynamic changes in their nuclear position and gene expression. To address this issue, we systematically analyzed the cDNA profiles of a large number of single progenitor cells at the mid-embryonic stage in mouse. By cluster analysis and in situ hybridization, we have identified a set of genes that distinguishes between the apical and basal progenitors. Despite their relatively homogeneous global gene expression profiles, the apical progenitors exhibit highly variable expression patterns of Notch signaling components, raising the possibility that this causes the heterogeneous division patterns of these cells. Furthermore, we successfully captured the nascent state of basal progenitor cells. These cells are generated shortly after birth from the division of the apical progenitors, and show strong expression of the major Notch ligand delta-like 1, which soon fades away as the cells migrate in the ventricular zone. We also demonstrated that attenuation of Notch signals immediately induces differentiation of apical progenitors into nascent basal progenitors. Thus, a Notch-dependent feedback loop is likely to be in operation to maintain both progenitor populations.
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Modules G2 and G3 are enriched in SZi, and G3 is enriched for genes marking Svet1+ IPs in E14 mouse SZ.
“Modules G2 and G3 are enriched in the SZi (Fig. 3d, white bars in bottom two rows), and G3 is enriched for genes marking Svet1+ IPs in E14 mouse SZ43, including ELAVL4, LRP8, NEUROD1, NRN1, SLC17A6, SSTR2, and TP53INP1.”
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- Authors
- Kawaguchi, A., Ikawa, T., Kasukawa, T., Ueda, H. R., Kurimoto, K., Saitou, M., & Matsuzaki, F.
- Affiliations
- RIKEN (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Kawaguchi, Ayano
- Matsuzaki, Fumio
- ORCID
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2008-09-15
- Volume
- 135
- Issue
- 18
- Pages
- 3113-3124
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2141932458
- Cited by
- 193
- References
- 40
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 4 · 2021: 13 · 2020: 13 · 2019: 9 · 2018: 9 · 2017: 12 · 2016: 10 · 2015: 12 · 2014: 13 · 2013: 15 · 2012: 13
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (CREST)
- Japan Society for the Promotion of Science (18680030, 15700264, CREST)
- Japan Science and Technology Agency (CREST)
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- neural progenitor cells, apical progenitors, basal progenitors, Notch signaling, Delta-like 1, Notch ligands, progenitor heterogeneity, brain development, progenitor cell differentiation, single-cell gene expression profiling
- MeSH terms
- Animals, Embryo, Mammalian, Immunohistochemistry, Mammals, Mice, Inbred Strains, Nervous System, Neurons, Stem Cells, Signal Transduction, Biomarkers, Cluster Analysis, Prosencephalon, In Situ Hybridization, DNA, Complementary, Gene Expression Regulation, Developmental, Cell Lineage, Gene Expression Profiling, Organogenesis, Mice, Receptors, Notch
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