Pericyte structure and distribution in the cerebral cortex revealed by high-resolution imaging of transgenic mice

Abstract

Pericytes are essential for normal brain function, but many aspects of their physiology remain enigmatic due to a lack of tools to genetically target this cell population. Here, we characterize brain pericytes using two existing Cre-recombinase driver mouse lines that can serve distinct purposes in cerebrovascular research. One line expresses an inducible version of Cre under the NG2 proteoglycan promoter, which provides the sparse labeling necessary to define the morphology of single cells. These mice reveal structural differences between pericytes adjacent to arterioles versus those broadly distributed in the capillary bed that may underlie differential roles in control of vessel caliber. A second line expresses Cre constitutively under the platelet-derived growth factor receptor β promoter and provides continuous, highly specific and near-complete labeling of pericytes and myocytes along the entire cerebrovasculature. This line provides a three-dimensional view of pericyte distribution along the cortical angioarchitecture following optical clearing of brain tissue. In combination with recent reporter lines for expression of optogenetic actuators and activity-sensitive probes, these mice may be key tools for studying pericyte biology in the intact brain.

Dynamic Remodeling of Pericytes In Vivo Maintains Capillary Coverage in the Adult Mouse Brain

“…As in past studies, we observed a heterogeneity of mural cell types, ranging from ring-shaped smooth muscle cells on arterioles to pericytes with varying degrees of vessel coverage on pre-capillary arterioles and capillaries (Grant et al, 2017; Hartmann et al, 2015). In this study, we focused on pericytes adorning the mid-capillary regions (Figure 1C).…”

“…Recent high-resolution optical imaging studies have shown that brain capillary pericytes are organized as a cellular chain along the capillary bed (Hartmann et al, 2015; Hill et al, 2015). Each pericyte extends thin, elongated processes from distinct ovoid cell bodies to contact and communicate with multiple underlying endothelial cells (Allt and Lawrenson, 2001).…”

CD146 coordinates brain endothelial cell–pericyte communication for blood–brain barrier development

“…Confocal images were obtained with a Zeiss LSM 880 imaging system under a 63× water-immersion objective. Cerebral capillaries, precapillary arterioles, and postcapillary venules were identified according to features established in earlier publications (5,43,44) and briefly as follows: (i) αSMA-negative vessels with a vascular lumen diameter < 10 μm were identified as capillaries; (ii) αSMA-positive vessels terminating before αSMA-negative capillaries were identified as precapillary arterioles; and (iii) αSMA-negative vessels with a vascular lumen diameter 10-20 μm were identified as postcapillary venules.…”

Pericytes of the neurovascular unit: key functions and signaling pathways

“…Recent studies of the cortical angioarchitecture in mice expressing fluorescent proteins under control of the NG2 and PDGFRβ promoters have identified several pericyte subpopulations including VSMC-pericyte hybrid on pre-capillary arterioles, thin strand helical mid-capillary pericyte, and mesh pericyte with a stellate morphology on post-capillary arterioles and venules 19,20 . Future single-cell RNA-seq and proteomic studies as used successfully to characterize subpopulations of cortical progenitor cells 23 and drug resistant tumor cells 24 , may also contribute to better understanding of different pericyte subtypes.…”