Abnormal development of genetically normal fetal hematopoietic stem cells in steel mutant mouse fetuses.

The role and possible transplantability of the early hematopoietic microenvironment was investigated by transplacental inoculation of fetal liver cells from normal donors into steel mutant early fetuses. Donor hematopoietic stem cells were able to lodge in the livers of recipients and to progress to the bone marrow postnatally. However, self-renewal of stem cells and production of differentiated blood cells was very limited in extent and duration after transplantation into mildly anemic steel as compared with Wv/+ heterozygotes. The microenvironmental defect known to exist (albeit undefined) in steel and not in W mutants thus adversely affects proliferation and differentiation of stem cells from the very inception of hepatic hematopoiesis and is not correctable by introducing normal stromal cells under the conditions of the experiment.