Determination and differentiation of heamtopoietic stem cell toward T, B and myeloid cell lineages

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By using the multilineage progenitor (MLP) assay, which is able to determine the developmental capability of hematopoietic progenitors toward myeloid (M), T and B cell lineages, we have identified various types of progenitors in murine fetal liver (FL). The progenitor types detected were multipotent progenitors (p-MTB), bipotent progenitors generating M and T cells (p-MT) or M and B cells (p-MB), and unipotent progenitors generating M(p-M), T(p-T) or B(p-B) cells. Since p-TB type was defective, p-T and p-B were thought to be derived from p-MTB via p-MT and p-MB, respectively. These findings provided an opportunity to reconsider the process of hematopoiesis; it is improbable that the lineage commitment progresses stochastically, but it should progress deterministically. It was further shown that p-T emerge ontogenically earlier than p-B in FL, and moreover that all six types of progenitors are already produced in the aorta-gonad-mesonephros (AGM) region of day 10 fetuses. Although the p-MTB in AGM region do not have long-term reconstitution (LTR) activity, these p-MTB was found to acquire the LTR activity by culturing with a stromal cell line. Thymic earliest p-T are still multipotent in that they are able to generate dendritic cell (DC) and NK cells. These DC and NK potentials are release with the progress of intrathymic developmental stages.