Clonal and systemic analysis of long-term hematopoiesis in the mouse

Craig T. Jordan, Ihor R. Lemischka

    Research output: Contribution to journalArticlepeer-review

    Abstract

    We have analyzed the temporal in vivo fate of 142 individual stem cell clones in 63 reconstituted mice. Long-term sequential analyses of the four major peripheral blood lineages, obtained from animals engrafted with genetically marked stem cells, indicate that developmental behavior is primarily a function of time. As such, the first 4-6 months post-engraftment is characterized by frequent fluctuations in stem cell proliferation and differentiation behavior. Gradually, a stable hematopoietic system emerges, dominated by a small number of totipotent clones. We demonstrate that single stem cell clones are sufficient to maintain hematopoiesis over the lifetime of an animal and suggest that mono- or oligoclonality may be a hallmark of long-term reconstituted systems. A model is proposed, wherein lineage-restricted differentiation and dramatic clonal flux are consequences of mechanisms acting on an expanding pool of totipotent cells and are not indicative of intrinsically distinct stem cell classes.
    Original languageEnglish
    Pages (from-to)220-232
    Number of pages12
    JournalGenes and development
    Volume4
    Issue number2
    Publication statusPublished - 1990

    Keywords

    • Clonal analysis
    • Developmental behavior
    • Hematopoiesis
    • Stem cells

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