Newly discovered base barrier cells provide compartmentalization of choroid plexus, brain and CSF

Abstract

ABSTRACTThe choroid plexus (ChP) is a highly understudied structure of the central nervous system (CNS). The structure hangs in the brain ventricles, is composed of an epithelial cell layer, which produces the cerebrospinal fluid (CSF) and forms the blood-CSF barrier. It encapsulates a stromal mix of fenestrated capillaries, fibroblasts and a broad range of immune cells. Here, we report that the ChP base region harbors unique fibroblasts that cluster together, are connected by tight junctions and seal the ChP stroma from brain and CSF, thereby forming ChP base barrier cells (ChP BBCs). ChP BBCs are derived from meningeal mesenchymal precursors, arrive early during embryonic development, are maintained throughout life and are conserved across species. Moreover, we provide transcriptional profiles and key markers to label ChP BBCs and observe a striking transcriptional similarity with meningeal arachnoid barrier cells (ABCs). Finally, we provide evidence that this fibroblast cluster functions as a barrier to control communication between CSF and the ChP stroma and between the latter and the brain parenchyma. Moreover, loss of barrier function was observed during an inflammatory insult. Altogether, we have identified a novel barrier that provides functional compartmentalization of ChP, brain and CSF.GRAPHICAL ABSTRACTNewly discovered base barrier cells provide compartmentalization of choroid plexus, brain and CSFThe choroid plexus (ChP) hangs in the brain ventricles and is composed of an epithelial cell layer which produces the cerebrospinal fluid (CSF) and forms the blood-CSF barrier. The ChP epithelial cells are continuous with the ependymal cells lining the ventricle wall. At this base region, we identified and characterized a novel subtype of fibroblasts coined the ChP base barrier cells (BBCs). ChP BBCs express tight junctions (TJs), cluster together and seal the ChP stroma from CSF and brain parenchyma. The subarachnoid space (SAS) CSF penetrates deep into choroid plexus invaginations where it is halted by ChP BBCs.Abbreviations: E9-16.5 (embryonic day 9-16.5); P1-4 (postnatal day 1-4).