Mar 24, 2020

Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map

Nature Neuroscience
Omer Ali BayraktarDavid H. Rowitch

Abstract

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.

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Mentioned in this Paper

Cerebral Cortex
Neuroglia
Gene Expression
In Situ
Organ Component Layer
Gene Expression Profiling
Patterns
Spatial Analysis
Sequence Determinations, RNA
Laboratory mice

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