Human development has long been seen as a one-way street. During gestation, stem cells were thought to develop into a succession of ever more specialized cells. As Dr. R. Ariel Gomez has discovered, the final identity of these cells is not as definite as once thought. “The identity of many cell types is in a constant state of flux,” Gomez says.
Gomez, a professor of pediatrics who also serves as the University’s vice president for research and graduate studies, specializes in the juxtaglomerular (JG) cell. This is a highly specialized cell that in adults resides in the glomerulal area of the kidney and produces renin, a substance that increases blood pressure. Renin is essential for maintaining our fluids and electrolytes at healthy levels.
Working with colleagues Dr. Maria Sequeira Lopez and Ellen Pentz from the Department of Pediatric Nephrology, Gomez tracked the lineage of the JG cell back to its ancestor, a renin-producing progenitor cell that is widely distributed in the embryo. They also discovered that this progenitor cell evolves into a variety of different cell types besides the JG cell, including smooth muscle cells that line the blood vessels and cells that appear in the adrenal gland and other tissues.
Under normal conditions, there are enough JG cells producing renin to ensure that blood pressure remains at proper levels, but these cells alone cannot meet the demand in an emergency. “We discovered that when the body is threatened and blood pressure drops, those smooth muscle and adrenal cells derived from the renin progenitor return to an earlier type and produce renin,” says Gomez. “It is as if they have memory. We’re interested in cues in their immediate environment that cause them to revert.”
Gomez’s target is deep within the nucleus of the cell, in the chromatin scaffold that holds its DNA in place. A gene is expressed when the lattice around it opens up and allows the factors that transcribe the gene’s formula for a particular protein to come in contact with it. Gomez and his colleagues are working to pinpoint the factors that open the lattice around the renin gene in smooth muscle cells.
In Gomez’s view, the plasticity of the renin cells confers an evolutionary advantage. “It’s an efficient way of providing additional renin-producing capacity exactly when it’s needed,” he says. This dual identity also suggests the possibility of new therapies. “If we can describe the process by which cells revert to their renin-producing ancestor,” he notes, “it will open new possibilities for cell-based therapies in general and in the treatment of people with kidney and blood pressure diseases in particular.”
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