Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex
Open accessAbstract
Building a brain: The human brain is built in an inside-out manner as a series of layers. Although progenitor cells spin off new neurons in a seemingly organized fashion, the devil is in the details. Nowakowski et al. analyzed the transcriptomes of single cells from the developing brain to elucidate the hidden complexity of brain construction. For each cell, its position within the brain matters, as well as what type of neuron is being made at what point during overall development. These individual expression patterns result in organized diversity in the brain's cortex. Science , this issue p. 1318
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NPAS3 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 Nowakowski et al. 2017
The paper’s account of its single-cell RNA-seq analysis describes multiple cell types and developmental stages, but it does not report NPAS3 expression in those cells. Searches of our copy for “NPAS3” and for NPAS3 expression across developing-brain cell types found no passage addressing the gene-specific claim. (LLM, conf=0.72)
Experimental — accuracy not yet measuredIn 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 Nowakowski et al. 2017
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Experimental — accuracy not yet measuredContinuous trajectories appear in brain development and in adult differentiating populations, including oligodendrocyte lineage cells and newborn dentate gyrus granule cells.
“Continuous trajectories occur during brain development (Nowakowski et al., 2017) and in differentiating cell populations in the adult, such as oligodendrocyte lineage cells (Marques et al., 2016) or newborn granule cells in the dentate gyrus of the hippocampus (Habib et al., 2016).”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Nowakowski et al., 2017
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Single cell epigenomic atlas of the developing human brain and organoids
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Molecular Logic of Cellular Diversification in the Mammalian Cerebral Cortex
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- Authors
- Nowakowski, T. J., Bhaduri, A., Pollen, A. A., Alvarado, B., Mostajo-Radji, M. A., Di Lullo, E., Haeussler, M., Sandoval-Espinosa, C., Liu, S. J., Velmeshev, D., Ounadjela, J. R., Shuga, J., Wang, X., Lim, D. A., West, J. A., Leyrat, A. A., Kent, W. J., & Kriegstein, A. R.
- Affiliations
- University of California, San Francisco (US)
- Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA, USA.
- University of California, Santa Cruz (US)
- Standard BioTools (United States) (US)
- Corresponding author
- Nowakowski, Tomasz J.
- Bhaduri, Aparna
- Pollen, Alex A.
- Kriegstein, Arnold R.
- ORCID
- Venue
- Science
- Published
- 2017-12-08
- Volume
- 358
- Issue
- 6368
- Pages
- 1318-1323
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5991609
- OpenAlex
- W2772624269
- Semantic Scholar
- f6dfb471168febb2c0e2eeb9f9852360047e19ae
- Cited by
- 964
- References
- 38
- Citations by year
- 2026: 88 · 2025: 94 · 2024: 102 · 2023: 139 · 2022: 110 · 2021: 153 · 2020: 128 · 2019: 96 · 2018: 53
- FWCI
- 32.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (R01NS091544)
- Damon Runyon Cancer Research Foundation (DRG-2166-13)
- NIH (U01MH105989, R35NS097305)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- cortical development, neurogenesis, cell type diversity, mTOR signaling, outer radial glia, cortical topography, lineage-specific gene expression
- MeSH terms
- Cerebral Cortex, Humans, Neuroglia, Neurons, Telencephalon, Gene Expression Regulation, Developmental, Neurogenesis
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