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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Bayraktar, Omer Ali  ORCID logo  https://orcid.org/0000-0001-6055-277X
Bartels, Theresa 
Kleshchevnikov, Vitalii  ORCID logo  https://orcid.org/0000-0001-9110-7441
Martirosyan, Araks 

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.

Description

Keywords

Animals, Astrocytes, Brain Mapping, Cerebral Cortex, Humans, Mice, Neurons, Transcriptome

Journal Title

Nat Neurosci

Conference Name

Journal ISSN

1097-6256
1546-1726

Volume Title

23

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Wellcome Trust (108139/B/15/Z)
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF) (EQ2017B)
Wellcome Trust (108139/Z/15/Z)
Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)
European Research Council (789054)
Wellcome Trust (109142/Z/15/Z)
The study was supported by the Paul G. Allen Foundation Distinguished Investigator Program (E.M.U. and D.H.R.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (D.H.R., D.G. and G. C.), BRAIN initiative (1U01 MH105991 to D.G.) and National Institute of Health (1R01 MH109912 to D.G.; P01NS08351 to D.H.R.), National Institute of Health Research and the European Union Seventh Framework (to P.H.), NINDS Informatics Center for Neurogenetics and Neurogenomics (P30 NS062691 to G.C.), Wellcome Trust core support (M.H., O.A.B.), European Research Council (281961 to M.G.H.), Fonds Wetenschappelijk Onderzoek (G066715N and 1523014N to M.G.H.), Stichting Alzheimer Onderzoek (S#16025 to M.G.H.) and VIB Institutional Support and Tech Watch funding (to M.G.H.), Howard Hughes Medical Institute and the Wellcome Trust (to D.H.R.).