Renin cells are precursors for multiple cell types that switch to the renin phenotype when homeostasis is threatened.

Renin-synthesizing cells are crucial in the regulation of blood pressure and fluid-electrolyte homeostasis. Adult mammals subjected to manipulations that threaten homeostasis increase circulating renin by increasing the number of renin-expressing/-releasing cells. We hypothesize that the ability of adult cells to synthesize renin does not occur randomly in any cell type, depending instead on the cell's lineage. To determine the fate of renin-expressing cells, we generated knockin mice expressing cre recombinase in renin-expressing cells and crossed them with reporter mice. Results show that renin-expressing cells are precursors for a variety of cells that differentiate into non-renin-expressing cells such as smooth-muscle, epithelial, mesangial, and extrarenal cells. In the kidney, these cells retain the capability to synthesize renin when additional hormone is required to reestablish homeostasis: specific subpopulations of apparently differentiated cells are "held in reserve" to respond (repeatedly) by de-differentiating and expressing renin in response to stress, and re-differentiating when the crisis passes.

The embryo makes red blood cell progenitors in every tissue simultaneously with blood vessel morphogenesis.

During embryonic life, hematopoiesis occurs first in the yolk sac, followed by the aorto-gonado-mesonephric region, the fetal liver, and the bone marrow. The possibility of hematopoiesis in other embryonic sites has been suspected for a long time. With the use of different methodologies (transgenic mice, electron microscopy, laser capture microdissection, organ culture, and cross-transplant experiments), we show that multiple regions within the embryo are capable of forming blood before and during organogenesis. This widespread phenomenon occurs by hemo-vasculogenesis, the formation of blood vessels accompanied by the simultaneous generation of red blood cells. Erythroblasts develop within aggregates of endothelial cell precursors. When the lumen forms, the erythroblasts "bud" from endothelial cells into the forming vessel. The extensive hematopoietic capacity found in the embryo helps explain why, under pathological circumstances such as severe anemia, extramedullary hematopoiesis can occur in any adult tissue. Understanding the intrinsic ability of tissues to manufacture their own blood cells and vessels has the potential to advance the fields of organogenesis, regeneration, and tissue engineering.