Extraction of Distinct Neuronal Cell Types from within a Genetically Continuous Population
Open accessAbstract
Single-cell transcriptomics of neocortical neurons have revealed more than 100 clusters corresponding to putative cell types. For inhibitory and subcortical projection neurons (SCPNs), there is a strong concordance between clusters and anatomical descriptions of cell types. In contrast, cortico-cortical projection neurons (CCPNs) separate into surprisingly few transcriptomic clusters, despite their diverse anatomical projection types. We used projection-dependent single-cell transcriptomic analyses and monosynaptic rabies tracing to compare mouse primary visual cortex CCPNs projecting to different higher visual areas. We find that layer 2/3 CCPNs with different anatomical projections differ systematically in their gene expressions, despite forming only a single genetic cluster. Furthermore, these neurons receive feedback selectively from the same areas to which they project. These findings demonstrate that gene-expression analysis in isolation is insufficient to identify neuron types and have important implications for understanding the functional role of cortical feedback circuits.
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Kim et al. found that long-range connections from visual cortex layer 2/3 neurons correlate not with transcriptomic types but with gene expression differences within types.
“A recent study showed that long-range connections from visual cortex layer 2/3 neurons do not correlate with transcriptomic types but rather with within-type gene expression differences (Kim et al., 2020).”
From Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells (2020) · cites this paper as Kim et al., 2020
In mouse primary visual cortex, pyramidal cells projecting to different higher-order visual areas form a continuous transcriptomic population, despite some differentially expressed genes.
“For example, Retro-seq analysis of mouse primary visual cortical pyramidal cells projecting to different higher-order visual areas form a continuous transcriptomic population, although some differentially expressed genes were detected (Kim et al., 2020).”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Kim et al., 2020
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- Authors
- Kim, E. J., Zhang, Z., Huang, L., Ito-Cole, T., Jacobs, M. W., Juavinett, A. L., Senturk, G., Hu, M., Ku, M., Ecker, J. R., & Callaway, E. M.
- Affiliations
- Salk Institute for Biological Studies (US)
- University of California San Diego (US)
- Corresponding author
- Callaway, Edward M.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 107
- Issue
- 2
- Pages
- 274-282.e6
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC7381365
- OpenAlex
- W3023918693
- Cited by
- 103
- References
- 36
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 14 · 2023: 13 · 2022: 23 · 2021: 30 · 2020: 7 · 2019: 1 · 2018: 1
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health
- National Cancer Institute
- Brain Research Foundation
- National Eye Institute
- Brain and Behavior Research Foundation
- Life Sciences Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- single-cell transcriptomics, primary visual cortex, layer 2/3 neurons, cortical feedback, gene expression clusters, mouse visual system
- MeSH terms
- Animals, Cerebral Cortex, Feedback, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Neural Pathways, Neurons, Rabies virus, Visual Cortex, Gene Expression, Neocortex, Mice, Gene Knock-In Techniques, Transcriptome
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