New Pericytes in the Adult Brain Originate from a Previously Unrecognized Pericyte Precursor

Abstract

Pericytes are essential for maintaining the stability of CNS blood-vessels and the blood-brain- barrier. They are closely associated with endothelia and can be identified by a set of markers. New pericytes are required during neo-angiogenesis but how pericytes are generated in the adult brain is unknown. Here, we investigated neoplastic vascularization of the adult brain in a transgenic lineage-tracing model. We observed that mature pericytes largely originate from a newly identified precursor celltype, which is distinct from established brain cell-populations as evidenced by single-cell RNAseq studies. These precursors are characterized as pericyte marker-negative cells of non-hematopoietic origin, which are distant from blood-vessels and highly proliferative. Pericyte precursors emerge also in developmental angiogenesis and lineage ablation experiments in brain tumor models showed that they are necessary to generate new, mature pericytes supporting tumor expansion. Overall, pericyte precursors control vascular plasticity and provide an excellent therapeutic target for brain tumors.