The Wnt pathway co-receptor, Leucine Rich Repeat Containing G Protein-Coupled Receptor 5 (LGR5), labels tumor-prone stem cell populations in certain types of tissue. In this study, we show that ARID1A and PIK3CA mutations in LGR5⁺ cells result in renal angiosarcomas in adult mice. The tumors originate in the renal medulla. We further show that LGR5 labels SOX17⁺/CD31⁺/CD34⁺/CD133⁺/AQP1⁺/CD146⁺ endothelial progenitor cells within the descending vasa recta or straight arterioles of the kidney, which are specialized capillaries that maintain medullary osmotic gradients necessary for water reabsorption and the production of concentrated urine. LGR5⁺ endothelial progenitor cells are tightly associated with contractile pericytes within the descending vasa recta. Long-term in vivo lineage tracing revealed that LGR5⁺ cells give rise to renal medullary vasculature. We further show that LGR5⁺ cells are activated in response to ischemic kidney injury. Our findings uncover a physiologically relevant endothelial progenitor cell population within the kidney vasa recta.

Wnt 通路共受体，富含亮氨酸重复序列的 G 蛋白偶联受体 5 (LGR5) 标记某些类型组织中易患肿瘤的干细胞群。在这项研究中，我们发现 LGR5 ⁺细胞中的 ARID1A 和 PIK3CA 突变导致成年小鼠出现肾血管肉瘤。肿瘤起源于肾髓质。我们进一步表明，LGR5 标记 SOX17 ⁺ /CD31 ⁺ /CD34 ⁺ /CD133 ⁺ /AQP1 ⁺ /CD146 ⁺直肠降支或肾脏直小动脉内的内皮祖细胞，它们是维持水所需的髓质渗透梯度的特殊毛细血管重吸收和浓缩尿液的产生。LGR5⁺内皮祖细胞与下行直肠血管内的收缩性周细胞紧密相关。长期体内谱系追踪显示 LGR5 ⁺细胞产生肾髓质脉管系统。我们进一步表明，LGR5 ⁺细胞响应缺血性肾损伤而被激活。我们的研究结果揭示了肾血管直肠内生理相关的内皮祖细胞群。