Conservation and divergence of cortical cell organization in human and mouse revealed by MERFISH
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The human cerebral cortex has tremendous cellular diversity. How different cell types are organized in the human cortex and how cellular organization varies across species remain unclear. In this study, we performed spatially resolved single-cell profiling of 4000 genes using multiplexed error-robust fluorescence in situ hybridization (MERFISH), identified more than 100 transcriptionally distinct cell populations, and generated a molecularly defined and spatially resolved cell atlas of the human middle and superior temporal gyrus. We further explored cell-cell interactions arising from soma contact or proximity in a cell type–specific manner. Comparison of the human and mouse cortices showed conservation in the laminar organization of cells and differences in somatic interactions across species. Our data revealed human-specific cell-cell proximity patterns and a markedly increased enrichment for interactions between neurons and non-neuronal cells in the human cortex.
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After mapping each cell in the spatial transcriptomic dataset to subclasses and supertypes, there was concordance between expected and mapped spatial distributions; for example, excitatory IT subclasses were restricted to expected cortical layers and matched proportions observed in previous studies of neurotypical MTG tissue.
“After mapping each cell in the spatial transcriptomic dataset to subclasses and supertypes, we found concordance between expected and mapped spatial distributions; for example, excitatory intratelencephalic (IT) subclasses were restricted to expected cortical layers and matched proportions observed in previous studies of neurotypical MTG tissue17,50 (Extended Data Fig. 7f,g).”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [50]
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- Authors
- Fang, R., Xia, C., Close, J. L., Zhang, M., He, J., Huang, Z., Halpern, A. R., Long, B., Miller, J. A., Lein, E. S., & Zhuang, X.
- Affiliations
- Howard Hughes Medical Institute (US)
- Allen Institute for Brain Science (US)
- Corresponding author
- Fang, Rongxin
- Xia, Chenglong
- He, Jiang
- Zhuang, Xiaowei
- ORCID
- Venue
- Science
- Published
- 2022-07
- Volume
- 377
- Issue
- 6601
- Pages
- 56-62
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC9262715
- OpenAlex
- W4283718372
- Cited by
- 277
- References
- 54
- Citations by year
- 2026: 48 · 2025: 73 · 2024: 75 · 2023: 70 · 2022: 9 · 2021: 1 · 2018: 1
- FWCI
- 18.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (P30AG066509)
- National Institute of Mental Health (R01MH113094, U19MH114830)
- 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 › Biophysics › Cell Image Analysis Techniques
- Keywords
- human cerebral cortex, cell-cell interactions, human-mouse comparison, middle temporal gyrus, superior temporal gyrus, single-cell transcriptomics, laminar organization
- MeSH terms
- Animals, Cell Communication, Cerebral Cortex, Humans, Neurons, In Situ Hybridization, Fluorescence, Gene Expression Profiling, Mice, Single-Cell Analysis
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