The transcription factor Pu.1 plays two key roles in the production of red blood cells: It promotes the proliferation of red-cell progenitors and blocks their differentiation into mature red cells. In the August 19 online edition of PNAS, Michael Willcockson, Arthur Skoultchi, Ph.D., and colleagues describe the mechanisms that control the expression of Pu.1 in red-cell progenitors. The researchers found that the transcription factor Runx1 regulates Pu.1 through a DNA sequence known as the “URE” (upstream regulatory element) in red-cell progenitors. Forced expression of either Runx1 or Pu.1 led to immortalization of mouse erythroid progenitors. Their finding suggests that manipulating Runx1 or Pu.1 expression in human red-cell progenitors could lead to a novel source of cells, which could be expanded indefinitely and triggered at will to differentiate into mature red cells for blood transfusions or other therapeutic applications. Dr. Skoultchi is professor and chair of cell biology and the Judith and Burton P. Resnick Chair in Cell Biology at Einstein. The study’s lead author was Michael Willcockson, an M.D./Ph.D. student in Dr. Skoultchi’s lab.