Requirement for erythroblast-macrophage protein (Emp) in definitive erythropoiesis.
Emp, erythroblast-macrophage protein was initially identified as a mediator of erythroblast-macrophage interactions during erythroid differentiation. More recent studies have shown that targeted disruption of Emp leads to abnormal erythropoiesis in the fetal liver, and fetal demise. To further address the activity of Emp in the hematopoietic lineage in adult bone marrow, we conducted fetal liver HSC reconstitution assay. Emp null fetal liver cells were transplanted into lethally irradiated wild-type sibling mice, and assessed the erythropoietic activity. We found that Emp null cells rescued lethally irradiated mice with efficiency comparable to that of wild-type cells. However, the recipients of Emp null cells showed abnormal erythropoiesis as indicated by the presence of persistent anemia, extensive extramedullary erythropoiesis, and increased apoptosis of erythroid precursors. Extramedullary erythropoiesis suggests perturbed interactions between the Emp-deficient hematopoietic cells and the wild-type niche. Furthermore, in spleen colony-forming unit assays, proliferation rates of the Emp null cells were greater than those of the wild-type cells. Similarly, in vitro burst-forming unit-erythroid and colony-forming unit-erythroid assays showed increased erythroid colony numbers from Emp null livers. Morphologic examination showed that Emp null CFU-E-derived erythroblasts were immature compared to those derived from wild-type CFU-Es, suggesting that loss of Emp function in erythroid cells results in impaired proliferation and terminal differentiation. These results demonstrate that Emp plays a cell intrinsic role in the erythroid lineage.
Soni
Shivani
S
Department of Medicine, Center of Cell Biology, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA.
Bala
Shashi
S
Hanspal
Manjit
M
D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000502:physiology*; D041905:Erythroid Cells / Q000166:cytology; D015672:Erythroid Precursor Cells / Q000166:cytology; D004920:Erythropoiesis; D018380:Hematopoietic Stem Cell Transplantation; D008099:Liver / Q000166:cytology; D051379:Mice; D014916:Whole-Body Irradiation
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C513480:erythroblast macrophage protein, mouse