Langen Urs H, Pitulescu Mara E, Kim Jung Mo, Enriquez-Gasca Rocio, Sivaraj Kishor K, Kusumbe Anjali P, Singh Amit, Di Russo Jacopo, Bixel M Gabriele, Zhou Bin, Sorokin Lydia, Vaquerizas Juan M, Adams Ralf H
Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
Max Planck Institute for Molecular Biomedicine, Research Group Regulatory Genomics, D-48149 Münster, Germany.
Nat Cell Biol. 2017 Mar;19(3):189-201. doi: 10.1038/ncb3476. Epub 2017 Feb 20.
Blood vessels in the mammalian skeletal system control bone formation and support haematopoiesis by generating local niche environments. While a specialized capillary subtype, termed type H, has been recently shown to couple angiogenesis and osteogenesis in adolescent, adult and ageing mice, little is known about the formation of specific endothelial cell populations during early developmental endochondral bone formation. Here, we report that embryonic and early postnatal long bone contains a specialized endothelial cell subtype, termed type E, which strongly supports osteoblast lineage cells and later gives rise to other endothelial cell subpopulations. The differentiation and functional properties of bone endothelial cells require cell-matrix signalling interactions. Loss of endothelial integrin β1 leads to endothelial cell differentiation defects and impaired postnatal bone growth, which is, in part, phenocopied by endothelial cell-specific laminin α5 mutants. Our work outlines fundamental principles of vessel formation and endothelial cell differentiation in the developing skeletal system.
哺乳动物骨骼系统中的血管通过产生局部微环境来控制骨形成并支持造血作用。虽然最近已证明一种称为H型的特殊毛细血管亚型在青少年、成年和衰老小鼠中耦合血管生成和成骨作用，但对于早期发育性软骨内骨形成过程中特定内皮细胞群体的形成了解甚少。在这里，我们报告胚胎期和出生后早期的长骨含有一种特殊的内皮细胞亚型，称为E型，它强烈支持成骨细胞谱系细胞，并随后产生其他内皮细胞亚群。骨内皮细胞的分化和功能特性需要细胞与基质的信号相互作用。内皮整合素β1的缺失会导致内皮细胞分化缺陷和出生后骨生长受损，内皮细胞特异性层粘连蛋白α5突变体部分模拟了这种情况。我们的工作概述了发育中的骨骼系统中血管形成和内皮细胞分化的基本原理。
