Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex
Open accessAbstract
The human cerebral cortex depends for its normal development and size on a precisely controlled balance between self-renewal and differentiation of diverse neural progenitor cells. Specialized progenitors that are common in humans but virtually absent in rodents, called outer radial glia (ORG), have been suggested to be crucial to the evolutionary expansion of the human cortex. We combined progenitor subtype-specific sorting with transcriptome-wide RNA sequencing to identify genes enriched in human ORG, which included targets of the transcription factor neurogenin and previously uncharacterized, evolutionarily dynamic long noncoding RNAs. Activating the neurogenin pathway in ferret progenitors promoted delamination and outward migration. Finally, single-cell transcriptional profiling in human, ferret and mouse revealed more cells coexpressing proneural neurogenin targets in human than in other species, suggesting greater neuronal lineage commitment and differentiation of self-renewing progenitors. Thus, we find that the abundance of human ORG is paralleled by increased transcriptional heterogeneity of cortical progenitors.
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Outer radial glia cells are enriched in targets of the neurogenin-family, proneural genes highly expressed in mouse intermediate progenitor cells but not mouse radial glia cells.
“oRG cells were enriched in targets of the neurogenin-family, which are proneural genes that are highly expressed in mouse iPCs but not mouse RG cells.”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Johnson et al., 2015
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References 51 · Cited by 288
- Authors
- Johnson, M. B., Wang, P. P., Atabay, K. D., Murphy, E. A., Doan, R. N., Hecht, J. L., & Walsh, C. A.
- Affiliations
- Boston Children's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Broad Institute (US)
- Corresponding author
- Walsh, Christopher A
- Venue
- Nature Neuroscience
- Published
- 2015-03-03
- Volume
- 18
- Issue
- 5
- Pages
- 637-646
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5568903
- OpenAlex
- W2032321721
- Cited by
- 288
- References
- 51
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 16 · 2023: 23 · 2022: 22 · 2021: 35 · 2020: 32 · 2019: 24 · 2018: 29 · 2017: 32 · 2016: 34 · 2015: 18 · 2013: 1
- FWCI
- 15.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (1s10rr028832-01)
- National Institute of Neurological Disorders and Stroke (R01NS032457)
- National Center for Research Resources (S10 RR028832, 1S10RR028832-01)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
- 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 › Single-cell and spatial transcriptomics
- Keywords
- outer radial glia, neurogenin, long non-coding RNA, progenitor self-renewal, ferrets, mice, cortical expansion, outward migration, single-cell transcriptomics
- MeSH terms
- Animals, Cerebral Cortex, Ferrets, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Sequence Homology, Nucleic Acid, Species Specificity, Transcription, Genetic, Sequence Alignment, Sequence Analysis, RNA, Gene Expression Regulation, Developmental, Gene Expression Profiling, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Neural Stem Cells, Single-Cell Analysis, RNA, Long Noncoding, Ependymoglial Cells
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