Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Dec;85(23):9278–9282. doi: 10.1073/pnas.85.23.9278

Fetal hemoglobin synthesis in vivo: direct evidence for control at the level of erythroid progenitors.

T Umemura 1, A Al-Khatti 1, T Papayannopoulou 1, G Stamatoyannopoulos 1
PMCID: PMC282722  PMID: 2461566

Abstract

To test directly whether the control of fetal hemoglobin (HbF) in the adult takes place at the level of erythroid progenitors or at the level of erythroblasts, we treated animals with high doses of erythropoietin and examined the effects of this manipulation on the globin gene programs of erythroid progenitors. We found that administration of erythropoietin produced a rapid expansion of all classes of erythroid progenitors. Almost all the expansion of colony-forming units-erythroid and 46-56% of erythroid clusters was due to the increase of HbF-programmed erythroid progenitors. The expansion of HbF-programmed erythroid progenitors was followed, 2-3 days later, by a wave of reticulocytes containing HbF in the peripheral blood. These results provide direct in vivo evidence that fetal-globin expression in the adult is controlled at the level of erythroid progenitors.

Full text

PDF
9278

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adamson J. W., Torok-Storb B., Lin N. Analysis of erythropoiesis by erythroid colony formation in culture. Blood Cells. 1978;4(1-2):89–103. [PubMed] [Google Scholar]
  2. Al-Khatti A., Veith R. W., Papayannopoulou T., Fritsch E. F., Goldwasser E., Stamatoyannopoulos G. Stimulation of fetal hemoglobin synthesis by erythropoietin in baboons. N Engl J Med. 1987 Aug 13;317(7):415–420. doi: 10.1056/NEJM198708133170704. [DOI] [PubMed] [Google Scholar]
  3. Chui D. H., Wong S. C., Enkin M. W., Patterson M., Ives R. A. Proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation. Proc Natl Acad Sci U S A. 1980 May;77(5):2757–2761. doi: 10.1073/pnas.77.5.2757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dover G. J., Boyer S. H. Quantitation of hemoglobins within individual red cells: asynchronous biosynthesis of fetal and adult hemoglobin during erythroid maturation in normal subjects. Blood. 1980 Dec;56(6):1082–1091. [PubMed] [Google Scholar]
  5. Dover G. J., Humphries R. K., Young N., Ley T., Boyer S., Charache S., Nienhuis A. Pharmacologic manipulation of fetal hemoglobin synthesis. Prog Clin Biol Res. 1985;191:447–454. [PubMed] [Google Scholar]
  6. Farquhar M. N., Turner P. A., Papayannopoulou T., Brice M., Nienhuis A. W., Stamatoyannopoulos G. The asynchrony of gamma- and beta-chain synthesis during human erythroid cell maturation. III. gamma- and beta-mRNA in immature and mature erythroid clones. Dev Biol. 1981 Jul 30;85(2):403–408. doi: 10.1016/0012-1606(81)90271-2. [DOI] [PubMed] [Google Scholar]
  7. Hanna I. R., Tarbutt R. G., Lamerton L. F. Shortening of the cell-cycle time of erythroid precursors in response to anaemia. Br J Haematol. 1969 Apr;16(4):381–387. doi: 10.1111/j.1365-2141.1969.tb00415.x. [DOI] [PubMed] [Google Scholar]
  8. Iscove N. N. The role of erythropoietin in regulation of population size and cell cycling of early and late erythroid precursors in mouse bone marrow. Cell Tissue Kinet. 1977 Jul;10(4):323–334. doi: 10.1111/j.1365-2184.1977.tb00300.x. [DOI] [PubMed] [Google Scholar]
  9. Papayannopoulou T. H., Brice M., Stamatoyannopoulos G. Stimulation of fetal hemoglobin synthesis in bone marrow cultures from adult individuals. Proc Natl Acad Sci U S A. 1976 Jun;73(6):2033–2037. doi: 10.1073/pnas.73.6.2033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Papayannopoulou T., Finch C. A. On the in vivo action of erythropoietin: a quantitative analysis. J Clin Invest. 1972 May;51(5):1179–1185. doi: 10.1172/JCI106911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Papayannopoulou T., Kalmantis T., Stamatoyannopoulos G. Cellular regulation of hemoglobin switching: evidence for inverse relationship between fetal hemoglobin synthesis and degree of maturity of human erythroid cells. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6420–6424. doi: 10.1073/pnas.76.12.6420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Papayannopoulou T., Vichinsky E., Stamatoyannopoulos G. Fetal Hb production during acute erythroid expansion. I. Observations in patients with transient erythroblastopenia and post-phlebotomy. Br J Haematol. 1980 Apr;44(4):535–546. doi: 10.1111/j.1365-2141.1980.tb08707.x. [DOI] [PubMed] [Google Scholar]
  13. Peschle C., Migliaccio A. R., Migliaccio G., Mavilio F., Rocca E., Petrini M., Mastroberardino G., Comi P., Giglioni B., Ottolenghi S. A model for hemoglobin F synthesis in adult life: evidence for regulation at the level of erythroblasts. Ann N Y Acad Sci. 1985;445:225–234. doi: 10.1111/j.1749-6632.1985.tb17192.x. [DOI] [PubMed] [Google Scholar]
  14. Stamatoyannopoulos G., Veith R., Galanello R., Papayannopoulou T. Hb F production in stressed erythropoiesis: observations and kinetic models. Ann N Y Acad Sci. 1985;445:188–197. doi: 10.1111/j.1749-6632.1985.tb17188.x. [DOI] [PubMed] [Google Scholar]
  15. Torrealba de Ron A., Papayannopoulou T., Stamatoyannopoulos G. Studies of Hb F in adult nonanemic baboons: Hb F expression in erythroid colonies decreases as the level of maturation of erythroid progenitors advances. Exp Hematol. 1985 Oct;13(9):919–925. [PubMed] [Google Scholar]
  16. Torrealba-de Ron A. T., Papayannopoulou T., Knapp M. S., Fu M. F., Knitter G., Stamatoyannopoulos G. Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine. Blood. 1984 Jan;63(1):201–210. [PubMed] [Google Scholar]
  17. Udupa K. B., Reissmann K. R. In vivo erythropoietin requirements of regenerating erythroid progenitors (BFU-e, CFU-e) in bone marrow of mice. Blood. 1979 Jun;53(6):1164–1171. [PubMed] [Google Scholar]
  18. Wagemaker G., Visser T. P. Erythropoietin-independent regeneration of erythroid progenitor cells following multiple injections of hydroxyurea. Cell Tissue Kinet. 1980 Sep;13(5):505–517. doi: 10.1111/j.1365-2184.1980.tb00491.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES