Journal
NATURE NEUROSCIENCE
Volume 23, Issue 4, Pages 500-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41593-020-0602-1
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Funding
- Life Sciences Research Fellowship
- Howard Hughes Medical Institute
- Wellcome Trust
- National Institute for Health Research (NIHR) Academic Clinical Fellowship
- Stichting Alzheiemer Onderzoek
- Paul G. Allen Foundation Distinguished Investigator Program
- Loulou Foundation
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- BRAIN initiative [1U01 MH105991]
- National Institutes of Health [1R01 MH109912, P01NS08351]
- NIHR
- European Union Seventh Framework
- National Institute of Neurological Disorders and Stroke Informatics Center for Neurogenetics and Neurogenomics [P30 NS062691]
- European Research Council [281961]
- Fonds Wetenschappelijk Onderzoek [G066715N, 1523014N]
- Stichting Alzheimer Onderzoek [16025]
- VIB Institutional Support
- Tech Watch funding
- MRC [MC_PC_17230] Funding Source: UKRI
- European Research Council (ERC) [281961] Funding Source: European Research Council (ERC)
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Although the cerebral cortex is organized into six excitatory neuronal layers, it is unclear whether glial cells show distinct layering. In the present study, we developed a high-content pipeline, the large-area spatial transcriptomic (LaST) map, which can quantify single-cell gene expression in situ. Screening 46 candidate genes for astrocyte diversity across the mouse cortex, we identified superficial, mid and deep astrocyte identities in gradient layer patterns that were distinct from those of neurons. Astrocyte layer features, established in the early postnatal cortex, mostly persisted in adult mouse and human cortex. Single-cell RNA sequencing and spatial reconstruction analysis further confirmed the presence of astrocyte layers in the adult cortex. Satb2 and Reeler mutations that shifted neuronal post-mitotic development were sufficient to alter glial layering, indicating an instructive role for neuronal cues. Finally, astrocyte layer patterns diverged between mouse cortical regions. These findings indicate that excitatory neurons and astrocytes are organized into distinct lineage-associated laminae. A new spatial transcriptomic approach reveals astrocyte heterogeneity across layers of the mammalian cerebral cortex. Astrocytes diversify into superficial-, mid- and deep-layer subtypes distinct from neuronal laminae, yet instructed by neuronal cues.
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