title: Molecular insights into stress erythropoiesis.
abstract: OBJECTIVE
  In addition to its essential role in baseline erythropoiesis, the hormone erythropoietin drives the erythropoietic response to hypoxic stress. A mechanistic understanding of stress erythropoiesis would benefit multiple clinical settings, and may aid in understanding leukemogenesis.
  
  
  RESULTS
  The spectrum of progenitors targeted by the erythropoietin receptor is broader during stress than during baseline erythropoiesis. Further, the requirement for erythropoietin receptor signaling is more stringent during stress. However, erythropoietin receptor signaling has been mostly studied in vitro, where it is difficult to relate signaling events to stress-dependent changes in erythroid homeostasis. Here we review advances in flow cytometry that allow the identification and study of murine erythroid precursors in hematopoietic tissue as they are responding to stress in vivo. The death receptor Fas and its ligand, FasL, are coexpressed by early splenic erythroblasts, suppressing erythroblast survival and erythropoietic rate. During stress, erythropoietin receptor signaling downregulates erythroblast Fas and FasL, consequently increasing erythropoietic rate.
  
  
  CONCLUSIONS
  Erythropoietic rate is regulated at least in part through the erythropoietin receptor-mediated survival of splenic early erythroblasts. Future research will delineate how multiple antiapoptotic pathways, potentially activated by the erythropoietin receptor, interact to produce the remarkable dynamic range of erythropoiesis.
authors.affiliation: Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01605, USA. merav.socolovsky@umassmed.edu
authors.forename: Merav
authors.initials: M
authors.lastname: Socolovsky
mesh_terms: D000818:Animals; D015672:Erythroid Precursor Cells / Q000166:cytology; D004920:Erythropoiesis; D007938:Leukemia / Q000209:etiology; D051379:Mice; D017467:Receptors, Erythropoietin / Q000502:physiology; D013312:Stress, Physiological
chemical_list: D017467:Receptors, Erythropoietin