Vascular Research Centre, Heart and Vascular Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.
Nat Commun. 2024 Aug 17;15(1):7097. doi: 10.1038/s41467-024-51637-7.
Converging evidence indicates that extra-embryonic yolk sac is the source of both macrophages and endothelial cells in adult mouse tissues. Prevailing views are that these embryonically derived cells are maintained after birth by proliferative self-renewal in their differentiated states. Here we identify clonogenic endothelial-macrophage (EndoMac) progenitor cells in the adventitia of embryonic and postnatal mouse aorta, that are independent of Flt3-mediated bone marrow hematopoiesis and derive from an early embryonic CXCR1 and CSF1R source. These bipotent progenitors are proliferative and vasculogenic, contributing to adventitial neovascularization and formation of perfused blood vessels after transfer into ischemic tissue. We establish a regulatory role for angiotensin II, which enhances their clonogenic and differentiation properties and rapidly stimulates their proliferative expansion in vivo. Our findings demonstrate that embryonically derived EndoMac progenitors participate in local vasculogenic responses in the aortic wall by contributing to the expansion of endothelial cells and macrophages postnatally.
越来越多的证据表明，胚胎外卵黄囊是成年老鼠组织中巨噬细胞和内皮细胞的来源。普遍观点认为，这些胚胎来源的细胞在出生后通过在分化状态下的增殖自我更新来维持。在这里，我们在胚胎和新生小鼠主动脉的外膜中鉴定出克隆形成的内皮-巨噬细胞（EndoMac）祖细胞，这些祖细胞不依赖于 Flt3 介导的骨髓造血，并且来源于早期胚胎的 CXCR1 和 CSF1R 来源。这些双能祖细胞具有增殖和血管生成能力，有助于外膜新生血管形成，并在转移到缺血组织后形成灌注血管。我们确定了血管紧张素 II 的调节作用，它增强了它们的克隆形成和分化特性，并在体内迅速刺激它们的增殖扩张。我们的研究结果表明，胚胎衍生的 EndoMac 祖细胞通过促进内皮细胞和巨噬细胞在出生后的扩张，参与到主动脉壁的局部血管生成反应中。
