Adult haematopoietic cells transplanted to sheep fetuses continue to produce adult globins

In man, several primates, sheep and goats, fetal haemoglobin (Hb F: α₂γ₂) is synthesized during the intra-uterine life, with a switch to adult haemoglobin (Hb A: α₂β ₂) production around birth. The mechanisms underlying the switches in globin gene expression are unknown. Studies of erythroid cell cultures suggest that haemoglobin switching is controlled at the level of haematopoietic progenitor cells^1,2. To test whether interactions between the haematopoietic environment and the haematopoietic progenitor cells have a role in the haemoglobin switch, we transplanted adult cells into unrelated sheep fetuses at a time of gestation when only fetal haemoglobin was being produced in the recipient cells. We report here that there was engraftment of the donor cells and bone marrow chimaeras were formed. The donor cells, proliferating and differentiating in the fetal environment, continued to produce adult haemoglobin. These results suggest that the fetal environment does not contain elements capable of switching the adult haematopoietic cells to a fetal programme of haemoglobin synthesis.