Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA.
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
J Cereb Blood Flow Metab. 2021 Sep;41(9):2185-2200. doi: 10.1177/0271678X211012836. Epub 2021 May 10.
Pericytes and endothelial cells share membranous interdigitations called "peg-and-socket" interactions that facilitate their adhesion and biochemical crosstalk during vascular homeostasis. However, the morphology and distribution of these ultrastructures have remained elusive. Using a combination of 3D electron microscopy techniques, we examined peg-and-socket interactions in mouse brain capillaries. We found that pegs extending from pericytes to endothelial cells were morphologically diverse, exhibiting claw-like morphologies at the edge of the cell and bouton-shaped swellings away from the edge. Reciprocal endothelial pegs projecting into pericytes were less abundant and appeared as larger columnar protuberances. A large-scale 3D EM data set revealed enrichment of both pericyte and endothelial pegs around pericyte somata. The ratio of pericyte versus endothelial pegs was conserved among the pericytes examined, but total peg abundance was heterogeneous across cells. These data show considerable investment between pericytes and endothelial cells, and provide morphological evidence for pericyte somata as sites of enriched physical and biochemical interaction.
周细胞和内皮细胞共享膜内凹陷结构,称为“钉和套”相互作用,有助于它们在血管稳态期间的黏附和生化串扰。然而,这些超微结构的形态和分布仍然难以捉摸。我们使用组合的三维电子显微镜技术,研究了小鼠脑毛细血管中的钉和套相互作用。我们发现,从周细胞延伸到内皮细胞的钉结构形态多样,在细胞边缘表现为爪状形态,远离边缘处则呈现出小球状肿胀。内皮细胞向周细胞内延伸的反向钉结构则较少,表现为更大的柱状突起。一个大规模的三维 EM 数据集显示,周细胞和内皮细胞的钉结构在周细胞体周围富集。在所检查的周细胞中,周细胞钉与内皮细胞钉的比例是保守的,但总钉数量在细胞间是不均匀的。这些数据表明周细胞和内皮细胞之间有相当大的投入,并为周细胞体作为物理和生化相互作用丰富的部位提供了形态学证据。