title: Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells.
abstract: The recent outbreak of Zika virus (ZIKV) in Brazil has been linked to substantial increases in fetal abnormalities and microcephaly. However, information about the underlying molecular and cellular mechanisms connecting viral infection to these defects remains limited. In this study we have examined the expression of receptors implicated in cell entry of several enveloped viruses including ZIKV across diverse cell types in the developing brain. Using single-cell RNA-seq and immunohistochemistry, we found that the candidate viral entry receptor AXL is highly expressed by human radial glial cells, astrocytes, endothelial cells, and microglia in developing human cortex and by progenitor cells in developing retina. We also show that AXL expression in radial glia is conserved in developing mouse and ferret cortex and in human stem cell-derived cerebral organoids, highlighting multiple experimental systems that could be applied to study mechanisms of ZIKV infectivity and effects on brain development.
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Nowakowski
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Pollen
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Di Lullo
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandoval-Espinosa
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Bershteyn
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: kriegsteina@stemcell.ucsf.edu.
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Kriegstein
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism; D004195:Disease Models, Animal; D005289:Ferrets; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism* / Q000821:virology*; D055495:Neurogenesis; D009457:Neuroglia / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D053586:Virus Internalization; D000071244:Zika Virus / Q000502:physiology*; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase