An Introduction to Erythropoiesis Approaches

Many experimental models have been used to study erythropoiesis. Even prior to the advent of the genetic manipulation of animal models, erythropoiesis was examined in the mouse, chicken, sheep, goat, and rabbit, among other vertebrates. Erythroid cell lines derived from human blood cancers were also very useful, as they could be genetically manipulated more easily than whole animals. Genetic models in the mouse, zebrafish, and frog have provided a plethora of information advancing our understanding of erythropoiesis, and remain gold standards in the field for studies of hemoglobin switching, and experiments to study authentic blood cell development. Mouse and human embryonic stem (ES) and induced pluripotent (iPS) cells can be differentiated to erythroid cells in culture, though their use is somewhat limited by their propensity to express only the embryonic and fetal globin genes. Some very useful cell lines have been developed by manipulating ES or fetal liver erythroid progenitor cells from knockout mouse models. In recent years, our understanding of erythropoiesis has improved, due to the ability to knock down genes in native human hematopoietic stem and progenitor cells derived from umbilical cord blood or bone marrow, and differentiate them ex vivo to the erythroid lineage. These native cells, and cell lines derived from them, are now providing essential information about human erythropoiesis, which is complementary to that obtained from animal studies. This review provides some perspective about the cell and animal models used to study erythropoiesis over the years.