Renin cells orchestrate a neuro-endocrine microenvironment of the kidney arterial tree in health and disease

Renin cells are essential for survival and serve as key regulators of blood pressure and fluid-electrolyte homeostasis. Their function and identity are dependent on signals from their local microenvironment afforded by neighboring cells and nerves. Whether and how renin cells contribute to the development and maintenance of this microenvironment remains unclear. Because renin cells are rare - 0.01 % of kidney cells - conventional histological approaches cannot capture their interaction with nerve fibers and surrounding cells within the nephron and its vasculature. Using high-resolution 3D imaging, cell-specific multicolor reporter mice, single-cell RNA-seq, and conditional gene deletions, we mapped how renin cells assemble within arterioles and communicate with axon fibers to organize the growth and orientation of the kidney arterioles during development and disease. This coinductive process is mediated by Ngf produced by renin cell precursors and is necessary for renin cell survival and innervation. Interestingly, renin enzymatic insufficiency elevates Ngf and drives arteriolar hypertrophy with aberrant axon sprouting and hyperinnervation. These findings indicate that renin cells regulate kidney neurovascular development, revealing them as active organizers of their local neuroregulatory microenvironment in health and disease.