Hemoglobin switching activity.
We describe observations that suggest the existence of an activity that induces the forward HbF-to-HbA switch. Studies in normal adult BFU-E cultures, in cultures of mutant BFU-E, and in cultures of cells from the neonatal and fetal stages of development reveal that the cells from various stages of ontogeny respond differently to this activity. Experiments using transfers of erythroid clones indicate that the hemoglobin switching activity acts on progenitors and that the interaction is of a direct nature. Our findings that the fetal BFU-E fail to respond whereas the neonatal and adult BFU-E do respond to the switching activity leads us to suggest that hemoglobin switching during ontogeny is controlled by a combined intrinsic/interactive mechanism. We propose that during ontogeny a locus becomes activated, the product of which (a receptor?) allows the cells to respond to their environment. Fetal cells do not switch because they cannot interact with their environment. The appearance of cellular receptors in erythroid progenitors after birth allows the progenitor cells to interact with their environment, and HbF-to-HbA switching ensues.
D000818:Animals; D004920:Erythropoiesis; D005319:Fetal Hemoglobin / Q000235:genetics*; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006441:Hemoglobin A / Q000235:genetics*; D006801:Humans; D012756:Sheep; D013789:Thalassemia / Q000378:metabolism
D006441:Hemoglobin A; D005319:Fetal Hemoglobin