Control of haemoglobin switching by a developmental clock?

• Published in: Nature (London) 1985-01, Vol.313 (6000), p.320-323
• Main Authors: Wood, W. G, Bunch, C, Kelly, S, Gunn, Y, Breckon, G
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone Marrow - embryology; Bone Marrow Cells; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Gestational Age; Globins - biosynthesis; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - metabolism; Hemoglobins - biosynthesis; Humanities and Social Sciences; letter; Liver - cytology; Liver - embryology; Molecular and cellular biology; multidisciplinary; Science; Science (multidisciplinary); Sheep; Thymus Gland - cytology; Thymus Gland - embryology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/313320a0

The pattern of haemoglobin production changes at the embryonic, fetal and postnatal stages of human development, reflecting the expression of different globin genes in both the α -like and β -like gene clusters 1,2 . Recent studies have identified alterations in the state of DNA methylation 3 and sensitivity to nuclease digestion 4 associated with developmental expression of the globin genes in red blood cell precursors, but the mechanism initiating these changes remains unknown. Despite the screening of large numbers of blood samples from newborn infants 5,6 , no mutants have been found which affect the timing of these changes (with one possible exception involving a chromosomal translocation 7 ), thus necessitating alternative approaches to analysing the cellular basis for the timing of haemoglobin switching. Although many mechanisms are possible, the initiation of the switch from fetal to adult haemoglobin could be regulated essentially either by a developmental clock inherent to haematopoietic stem cells or by an inductive enrivonment 8,9 , and in an attempt to distinguish between these possibilities, we have transplanted sheep fetal haematopoietic tissue into adult animals. Although previous experiments of this type produced conflicting results 10–12 , the accumulated results presented here demonstrate that the pattern of haemoglobin production after transplantation is determined largely by the gestational age of the fetal donor cells.