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Switch from fetal to adult hemoglobin is associated with a change in progenitor cell population

R S Weinberg, J D Goldberg, J M Schofield

    The Journal of Clinical Investigation
    |April 1, 1983
    PubMed

    Insights

    Hemoglobin switching from fetal to adult forms occurs at the cellular level. Fetal progenitors show a negative correlation between G gamma and beta-globin synthesis, replaced by adult progenitors with no correlation.

    Area of Science:

    • Hematology
    • Molecular Biology
    • Developmental Biology

    Background:

    • Hemoglobin switching is a critical developmental process, transitioning from fetal hemoglobin (HbF) to adult hemoglobin (HbA).
    • Understanding the cellular mechanisms governing this switch is crucial for comprehending normal erythropoiesis and related disorders.

    Purpose of the Study:

    • To investigate the cellular basis of the switch from fetal to adult hemoglobin production.
    • To analyze globin synthesis patterns in erythroid progenitor cells from newborns and adults at a clonal level.

    Main Methods:

    • Culture of erythroid progenitor cells from newborn and adult blood in methylcellulose with erythropoietin.
    • Labeling of individual erythroid colonies with [3H]leucine.
    • Analysis of globin synthesis patterns (gamma- and beta-globin) using gel electrophoresis and fluorography.

    Main Results:

    • Adult progenitor colonies showed no correlation between G gamma- and gamma- or beta-globin synthesis.
    • Newborn progenitor colonies exhibited distinct patterns: mature progenitors (day 14) showed a negative G gamma-beta correlation, while immature progenitors (days 17-21) showed no correlation.
    • These findings support a clonal model where fetal progenitors are gradually replaced by adult progenitors during development.

    Conclusions:

    • The cellular mechanism of hemoglobin switching involves the replacement of fetal progenitor cells with adult progenitor cells.
    • Fetal progenitors are characterized by a negative correlation between G gamma- and beta-globin synthesis, which is absent in adult progenitors.
    • This study provides evidence for a clonal basis of hemoglobin switching during human development.

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