Single-cell analysis of prenatal and postnatal human cortical development
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Abstract
We analyzed >700,000 single-nucleus RNA sequencing profiles from 106 donors during prenatal and postnatal developmental stages and identified lineage-specific programs that underlie the development of specific subtypes of excitatory cortical neurons, interneurons, glial cell types, and brain vasculature. By leveraging single-nucleus chromatin accessibility data, we delineated enhancer gene regulatory networks and transcription factors that control commitment of specific cortical lineages. By intersecting our results with genetic risk factors for human brain diseases, we identified the cortical cell types and lineages most vulnerable to genetic insults of different brain disorders, especially autism. We find that lineage-specific gene expression programs up-regulated in female cells are especially enriched for the genetic risk factors of autism. Our study captures the molecular progression of cortical lineages across human development.
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In the first postconceptional weeks, NPAS3 is expressed in radial glia cells, interneurons derived from ganglionic eminence, astrocytes, and intermediate progenitors; during later stages it is expressed in astrocytes, excitatory and inhibitory neurons.
“However, in the first postconceptional weeks, it is expressed in radial glia cells (RG), interneurons derived from ganglionic eminence (INT-CTX-GE), astrocytes, and Intermediate Progenitors (IPC [supplementary fig. S13e, Supplementary Material online; Nowakowski et al. 2017]); during later stages it is expressed in astrocytes, excitatory and inhibitory neurons (supplementary fig. S11f, Supplementa”
From The Human Accelerated Region HAR202 Controls <i>NPAS3</i> Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences (2024) · cites this paper as Velmeshev et al. 2023
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Experimental — accuracy not yet measuredNPAS3 is expressed in different cell types across human brain development.
“Additionally, the analysis of different databases of single-cell RNAseq in the human developing brain indicates that NPAS3 is expressed in different cell types across development (Nowakowski et al. 2017; Velmeshev et al. 2023; supplementary fig. S13e and f, Supplementary Material online).”
From The Human Accelerated Region HAR202 Controls <i>NPAS3</i> Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences (2024) · cites this paper as Velmeshev et al. 2023
The single-nucleus RNA sequencing analysis and Discussion describe gene expression across cortical cell types and developmental stages, but neither identifies NPAS3. Searches for “NPAS3” and “neuronal PAS domain protein 3” found no passage in our copy establishing its expression in different cell types across development. (LLM, conf=0.72)
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- Authors
- Velmeshev, D., Perez, Y., Yan, Z., Valencia, J. E., Castaneda-Castellanos, D. R., Wang, L., Schirmer, L., Mayer, S., Wick, B., Wang, S., Nowakowski, T. J., Paredes, M., Huang, E. J., & Kriegstein, A. R.
- Affiliations
- Duke University (US)
- University of California, San Francisco (US)
- Curio Bioscience, Palo Alto, CA 94303, USA.
- Vizgen Inc., Cambridge, MA 02138, USA.
- Heidelberg University (DE)
- University of California, Santa Cruz (US)
- Corresponding author
- Velmeshev, Dmitry
- Kriegstein, Arnold R.
- ORCID
- Venue
- Science
- Published
- 2023-10-13
- Volume
- 382
- Issue
- 6667
- Pages
- eadf0834-eadf0834
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC11005279
- OpenAlex
- W4387595265
- Cited by
- 204
- References
- 40
- Citations by year
- 2026: 68 · 2025: 81 · 2024: 46 · 2023: 8 · 2022: 1
- FWCI
- 18.09
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (K99-R00, NS083513)
- National Institute of Mental Health (RF1MH132662, K99/R00, K99MH131832, U01MH114825)
- National Human Genome Research Institute (U24HG002371)
- National Institute of Neurological Disorders and Stroke (NS083513, R35NS097305, P01NS083513, K99/R00)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- prenatal development, postnatal development, cortical excitatory neurons, interneurons, glial cell types, cerebral vasculature, single-nucleus RNA sequencing, chromatin accessibility, transcription factors, sex differences in gene expression, brain disorders
- MeSH terms
- Brain Diseases, Cerebral Cortex, Female, Humans, Infant, Newborn, Interneurons, Male, Neurons, Pregnancy, Risk Factors, Gene Regulatory Networks, Single-Cell Analysis
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