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Amendment history:
  • Correction (April 1981)

Research Article Free access | 10.1172/JCI110054

Control of the Simian Fetal Hemoglobin Switch at the Progenitor Cell Level

Blanche P. Alter, Benjamin T. Jackson, Jeffrey M. Lipton, George J. Piasecki, Pamela L. Jackson, Michele Kudisch, and David G. Nathan

Division of Hematology and Oncology of the Children's Hospital Medical Center and the Sidney Farber Cancer Institute, Boston, Massachusetts 02115

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

Department of Surgery, Boston University Medical Center and Boston Veteran's Administration Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118

Polly Annenberg Levee Hematology Center, Mount Sinai School of Medicine, New York 10029

Department of Medicine, Mount Sinai School of Medicine, New York 10029

Department of Pediatrics, Mount Sinai School of Medicine, New York 10029

Find articles by Alter, B. in: PubMed | Google Scholar

Division of Hematology and Oncology of the Children's Hospital Medical Center and the Sidney Farber Cancer Institute, Boston, Massachusetts 02115

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

Department of Surgery, Boston University Medical Center and Boston Veteran's Administration Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118

Polly Annenberg Levee Hematology Center, Mount Sinai School of Medicine, New York 10029

Department of Medicine, Mount Sinai School of Medicine, New York 10029

Department of Pediatrics, Mount Sinai School of Medicine, New York 10029

Find articles by Jackson, B. in: PubMed | Google Scholar

Division of Hematology and Oncology of the Children's Hospital Medical Center and the Sidney Farber Cancer Institute, Boston, Massachusetts 02115

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

Department of Surgery, Boston University Medical Center and Boston Veteran's Administration Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118

Polly Annenberg Levee Hematology Center, Mount Sinai School of Medicine, New York 10029

Department of Medicine, Mount Sinai School of Medicine, New York 10029

Department of Pediatrics, Mount Sinai School of Medicine, New York 10029

Find articles by Lipton, J. in: PubMed | Google Scholar

Division of Hematology and Oncology of the Children's Hospital Medical Center and the Sidney Farber Cancer Institute, Boston, Massachusetts 02115

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

Department of Surgery, Boston University Medical Center and Boston Veteran's Administration Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118

Polly Annenberg Levee Hematology Center, Mount Sinai School of Medicine, New York 10029

Department of Medicine, Mount Sinai School of Medicine, New York 10029

Department of Pediatrics, Mount Sinai School of Medicine, New York 10029

Find articles by Piasecki, G. in: PubMed | Google Scholar

Division of Hematology and Oncology of the Children's Hospital Medical Center and the Sidney Farber Cancer Institute, Boston, Massachusetts 02115

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

Department of Surgery, Boston University Medical Center and Boston Veteran's Administration Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118

Polly Annenberg Levee Hematology Center, Mount Sinai School of Medicine, New York 10029

Department of Medicine, Mount Sinai School of Medicine, New York 10029

Department of Pediatrics, Mount Sinai School of Medicine, New York 10029

Find articles by Jackson, P. in: PubMed | Google Scholar

Division of Hematology and Oncology of the Children's Hospital Medical Center and the Sidney Farber Cancer Institute, Boston, Massachusetts 02115

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

Department of Surgery, Boston University Medical Center and Boston Veteran's Administration Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118

Polly Annenberg Levee Hematology Center, Mount Sinai School of Medicine, New York 10029

Department of Medicine, Mount Sinai School of Medicine, New York 10029

Department of Pediatrics, Mount Sinai School of Medicine, New York 10029

Find articles by Kudisch, M. in: PubMed | Google Scholar

Division of Hematology and Oncology of the Children's Hospital Medical Center and the Sidney Farber Cancer Institute, Boston, Massachusetts 02115

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

Department of Surgery, Boston University Medical Center and Boston Veteran's Administration Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118

Polly Annenberg Levee Hematology Center, Mount Sinai School of Medicine, New York 10029

Department of Medicine, Mount Sinai School of Medicine, New York 10029

Department of Pediatrics, Mount Sinai School of Medicine, New York 10029

Find articles by Nathan, D. in: PubMed | Google Scholar

Published February 1, 1981 - More info

Published in Volume 67, Issue 2 on February 1, 1981
J Clin Invest. 1981;67(2):458–466. https://doi.org/10.1172/JCI110054.
© 1981 The American Society for Clinical Investigation
Published February 1, 1981 - Version history
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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 [3H]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 colonies produced only 15-35% beta. At the completion of the switch erythroblasts produced 100% beta globin, while progenitor-derived colonies produced as little as 40% beta chains. We conclude that the program of globin synthesis that characterizes the fetal switch is established at the level of erythroid progenitors. Fetal erythroid burst-forming units (BFU-E) dominate the marrow prior to the switch. The early switch period is heralded by the appearances of adult erythroid burst-forming units programmed to express increasing beta chain synthesis in colonies. By mid-switch a second class of adult erythroid progenitors capable of giving rise to fetal and adult hemoglobin synthesis in in vitro colonies becomes apparent. These shifting populations of erythroid progenitors with unique globin synthesis programs give rise to the erythroblasts that create the sigmoid pattern of the fetal to adult hemoglobin switch in the developing simian fetus.

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