Control of the simian fetal hemoglobin switch at the progenitor cell level

The Journal of Clinical Investigation
B P AlterD G Nathan

Abstract

This investigation was designed to define the cellular level at which the gamma to beta globin switch is established in the developing simian fetus in order to determine whether the switch is controlled by environmental influences within differentiating erythroid precursors or predetermined by the genetic program of erythroid progenitors. Samples of marrow and liver were obtained from rhesus fetuses throughout the switch period, and marrow was obtained from adult rhesus monkeys. Globin chain synthesis was then measured in differentiated erythroblasts and in erythroid progenitor-derived colonies grown in semisolid media. The relative rates of synthesis of gamma and beta chains were determined by the uptake of [(3)H]leucine into the respective chains separated by Triton gel electrophoresis and in some cases by urea carboxymethyl cellulose chromatography. Four periods of the switch were defined during fetal development. In the preswitch period both erythroblasts and progenitor-derived colonies produced <5% beta globin. In the early switch erythroblasts produced 5-15% beta globin, while progenitor-derived colonies produced 10-35% beta globin. In mid-switch erythroblasts synthesized 50% beta globin, whereas progenitor-derived coloni...Continue Reading

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Citations

Mar 3, 1983·The New England Journal of Medicine·D G Nathan, A Sytkowski
Sep 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·G StamatoyannopoulosT Papayannopoulou
Oct 1, 1982·The Journal of Clinical Investigation·R M MacklisD G Nathan
Apr 1, 1983·The Journal of Clinical Investigation·R S WeinbergB P Alter
Dec 1, 1986·The Journal of Clinical Investigation·B P AlterD G Nathan
Dec 16, 2011·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Colleen ByrnesJeffery L Miller
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