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

Bayraktar, O. A., Bartels, T., Holmqvist, S., Kleshchevnikov, V., Martirosyan, A., Polioudakis, D., ... & Brown, A. (2020). Nature Neuroscience, 23(4), 500-509. DOI: 10.1038/s41593-020-0602-1. PMID: 32203496.

Authors: Omer Ali Bayraktar 1 2 3, Theresa Bartels 4, Staffan Holmqvist 4, Vitalii Kleshchevnikov 5, Araks Martirosyan 6, Damon Polioudakis 7 8, Lucile Ben Haim 4, Adam M H Young 9, Mykhailo Y Batiuk 6, Kirti Prakash 4, Alexander Brown 10, Kenny Roberts 5, Mercedes F Paredes 11 12, Riki Kawaguchi 13, John H Stockley 4, Khalida Sabeur 4 11, Sandra M Chang 4 11, Eric Huang 12 14, Peter Hutchinson 9, Erik M Ullian 15, Martin Hemberg 5, Giovanni Coppola 7 13, Matthew G Holt 6, Daniel H Geschwind 7 8, David H Rowitch 16 17

Online: https://www.nature.com/articles/s41593-020-0602-1

Issue: Nature Neuroscience, 2020 Apr; 23(4):500-509.

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.

 

AUTHOR AFFILIATIONS

  1. Department of Paediatrics, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. ob5@sanger.ac.uk.
  2. Departments of Pediatrics and Neurosurgery, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  3. Wellcome Sanger Institute, Hinxton, UK.
  4. Department of Paediatrics, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  5. Wellcome Sanger Institute, Hinxton, UK.
  6. Laboratory of Glia Biology, VIB-KU Leuven Center for Brain and Disease Research, KU Leuven Department of Neuroscience, Leuven, Belgium.
  7. Departments of Neurology and Human Genetics, University of California Los Angeles, Los Angeles, CA, USA.
  8. Center for Autism Research and Treatment, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine,University of California Los Angeles, Los Angeles, CA, USA.
  9. Division of Academic Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  10. Sainsbury Wellcome Centre, University College London, London, UK.
  11. Departments of Pediatrics and Neurosurgery, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  12. Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
  13. Department of Psychiatry, University of California Los Angeles, Los Angeles, CA, USA.
  14. Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  15. Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.
  16. Department of Paediatrics, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  17. Departments of Pediatrics and Neurosurgery, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.