Building renin cells

Renin cells are crucial in the regulation of blood pressure, fluid-electrolyte homeostasis, and branching of the kidney vasculature. Renin cells originate from Foxd1+ stromal cells within the kidney and are precursors for arteriolar smooth muscle cells, pericytes, and mesangial cells. Recently, these cells have been shown to participate in the regeneration of injured mesangial cells and podocytes after experimentally induced glomerular injury. The cAMP and Notch pathways are major determinants of the acquisition and maintenance of the renin cell phenotype. Although significant advances have been made in identifying some of the mechanisms that govern the renin cell phenotype in vivo, the intricate mechanisms that control the identity and fate of renin cells have been difficult to ascertain. This is due in great part to the fact that renin cells are notoriously difficult to isolate and culture: the cells are scarce, 0.01 % of the total kidney cell mass, and when in culture they stop making renin after 48-72 h. To circumvent these problems, Drs. Gomez and Sequeira-Lopez developed a variety of genetically engineered mice and fluorescent cell models that allow tracing the lineage and fate of renin cells in vivo and in vitro. Because the cells are endogenously labeled with vital fluorescent markers they can be isolated to purity and their fate can be followed with precision as they change phenotypes.

To understand the molecular mechanisms responsible for the differentiation and maintenance of kidney renin cells we propose to induce the differentiation of progenitor cells at different stages of the developmental continuum from embryonic stem cells (ESCs) to renin cells.