Uncovering the epigenomic determinants of kidney vascular development [scRNA-seq]

Renin cells are essential for survival. They control the morphogenesis of the kidney arterioles, and the composition and volume of our extracellular fluid, arterial blood pressure, tissue perfusion, and oxygen delivery. Renin cells and associated arteriolar cells descend from FoxD1+ progenitor cells. The chromatin states and transcription factors that determine the differentiation of these cells into those that compose the kidney vasculature are unknown. To answer these questions, we isolated progenitors and their descendants at different embryonic and postnatal stages, and using integrated scRNA-seq and scATAC-seq established the developmental trajectory that leads to the mosaic of cells that compose the kidney arterioles. We constructed a single-cell atlas of chromatin accessibility and gene expression profiles-including the critical transcription factors that determine the identity and fate of the mosaic of cells that occur during kidney vascular development. Furthermore, we identified the factors that determine the elusive, myo-endocrine adult renin-secreting juxtaglomerular cell. Overall design: FoxD1+ cells, demarcating the renin lineage, were isolated at embryonic (E) day 12, E18, post-natal (P) day 5, and P30 and subjected to independent scRNA-seq and scRNA-seq to uncover the epigenomic determinants of kidney vascular development.