Hemoglobin switching in sheep: a comparison of the erythropoietin- induced
switch to HbC and the fetal to adult hemoglobin switch
JE Barker, JE Pierce and AW Nienhuis
Stimulation of sheep erythropoietic progenitor cells by erythropoietin
(epo) has been studied with regard to its effect on the pattern of
hemoglobin production. An analysis of hemoglobin (Hb) synthesis in BFU- E-
and CFU-E-derived colonies from fetuses either homozygous for HbA (AA)
(homozygous also for the beta c gene responsible for HbC production) or HbB
(BB) (lacking the beta c gene) indicated the following. Colonies derived
from precursor cells from 51- and 89-day fetuses exhibited small but
detectable increments of HbB synthesis with prolonged incubation in vitro.
This response was not dependent on the epo concentration. Erythropoietic
precursor cells from a 124-day BB fetus were already committed to HbB
synthesis, since HbF production was replaced by HbB on successive days in
vitro as erythroid colonies matured; this switch was not affected by
varying the epo concentration. In contrast, progenitor cells from a 124-day
AA fetus responded to higher doses of epo by forming colonies in which more
HbC was made at the expense of both HbF and HbA. Erythropoietic stress did
not result in induction of HbF in vivo or in erythroid colonies derived
from CFU-E in young adult BB sheep, whereas our prior studies had shown
induction of HbC synthesis under analogous conditions in colonies derived
from young adult AA sheep. We conclude that the epo-induced HbF (or HbA) to
HbC switch and the fetal to adult hemoglobin switch are regulated by
different mechanisms.
Volume 56,
Issue 3,
pp. 488-494,
09/01/1980
Copyright © 1980 by The American Society of Hematology
