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Early Fetal Liver Readily Repopulates B Lymphopoiesis in Adult Bone Marrow

Ko-Tung Chang, Ludek efc, Oskar Penák, Martin Vokurka, Emanuel Neas

Institute of Pathological Physiology, First Medical Faculty, Charles University, Prague, Czech Republic

Key Words. Fetal liver • Hematopoietic stem cell • B lymphopoiesis • Gene expression

Correspondence: Ko-Tung Chang, Ph.D., Institute of Pathological Physiology, First Medical Faculty, Charles University, U Nemocnice 5, 128 53 Prague, Czech Republic. Telephone: 420-2-2496-5934; Fax: 420-2-2491-2834; e-mail: kotungc{at}bcm.tmc.edu

Fetal liver (FL) becomes a major organ of hematopoiesis at mouse embryonic day (E) 11 and E12, when definitive hematopoietic stem cells, originating from the aorta-gonads-mesonephros region, colonize the hepatic tissue. Unipotent B-cell progenitors are very rare in FL by day 12, whereas erythropoiesis prevails. We have studied hematopoiesis in FL from different gestational ages, with special emphasis on B lymphopoiesis. The mRNA levels of selected liver-specific genes, hematopoietic lineage-specific genes, and genes for selected cytokines/hormones as well as for their receptors were evaluated by real-time polymerase chain reaction in FL from E12.5, E14.5, and E17.5, adult liver and adult bone marrow (BM). The level of B lineage–related gene expression in FL was very low at E12.5. There was also a significantly lower fraction of B220⁺ and CD19⁺ B cells in E12.5 FL compared with E17.5 FL. To analyze whether these differences reflect different stem cell potentials occurring during FL development, 10⁶ or 5 x 10⁶ of FL cells collected from embryos at E12.5 or E17.5 and those from adult BM were transplanted into sublethally irradiated (3- or 6-Gy) congenic mice. Short-term and long-term repopulation of B and T cells and granulocyte/macrophage lineages from donor FL or adult BM cells were evaluated in competition to adult hematopoiesis of sublethally irradiated recipients. In short-term repopulation, the transplantation of E12.5 FL cells resulted in a lower blood chimerism compared with that of E17.5 FL cells. However, the proportion of B lymphopoiesis exerted by E12.5 FL cells was not different from that of E17.5 FL or adult BM. This study demonstrates that E12.5 FL contains hematopoietic stem cells with fully developed B-cell repopulating capacity and that the developmental period of fetal hematopoiesis between E12.5 and E17.5 is not an obligatory phase for the adult B lymphopoiesis.

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