Curious about gene expression not covered in the paper? We made our atlases publically accessible via the Broad Institute Single Cell Portal! 2/11
Browse our single cell sequencing atlas
or our single nucleus sequencing atlas.
The choroid plexus blood-CSF barrier has remained a mystery for far too long! Our study led by
@NeilCDani1
and Rebecca Herbst, w/ Aviv Regev &
@naomi_habib
, is out today in
@CellCellPress
showcasing a cell atlas & exciting new findings. 1/11
Read it here
First, we had to develop micro-dissection approaches to isolate choroid plexus. Take a look at the striking morphologies of explants from the lateral (LV), third (3V) and fourth (4V) ventricle of the developing, adult and aging mouse brain. 3/11
Single cell sequencing shows that developing choroid plexuses comprise multiple cell types including epithelial, mesenchymal, endothelial, neuronal, glial & immune cells. Mapping the organization of neurons revealed a curious distribution of neuronal cell bodies. 4/11
Beyond the core cell types we identified a glia-like precursor population that gives rise to choroid plexus epithelial cells & neurons in the developing hindbrain. Shown here is a trajectory analysis that helped us map precursor & differentiated cell states in the paper. 5/11
Single nucleus sequencing revealed the same core cell types across all ventricles and ages. However, sub-clusters of these cells are regionalized (top) and age-specific (bottom) as visualized in the color-coded maps on the right. 6/11
Both lymphoid and myeloid immune cell populations are found across all ages. Of these, macrophages form the largest immune cell sub-type and significant shifts in gene expression mark functional maturation from embryonic to adult stages. 7/11
We found SARS-CoV-2 cell entry proteins expressed in multiple choroid plexus cell types across ventricles of the developing, adult and aging brains. Our results highlight the pressing need to better understand neuroimmune functions of the choroid plexus brain barrier. 8/11
Quite unexpectedly we found expression of blood-brain barrier proteins, such as claudin-5, in choroid plexus across all ages. Mapping claudin-5 expression in explants revealed subsets of vessels that are continuous with adjacent brain regions. 9/11
While choroid plexus is known to secrete signaling molecules into the CSF, we found significant cellular crosstalk within the choroid plexus. This Sankey plot maps ligand and receptor gene pairs highlighting potential communication axes within the tissue. 10/11