Showing papers by "Koichiro Ohmura published in 1997"

Direct evidence for the commitment of hematopoietic stem cells to T, B and myeloid lineages in murine fetal liver.

Abstract: We established an experimental system in vitro to examine the developmental capacity of individual hematopoietic progenitors to generate T, B and myeloid (M) cells. By using this system we analyzed the process of lineage commitment of hematopoietic progenitors in murine fetal liver (FL). It is known that small numbers of B and M cells, in addition to T cells, are generated in a co-culture of hematopoietic progenitors and a deoxyguanosine-treated fetal thymus (FT) lobe. We tried to enhance the growth of B and M cells by the addition of IL-7, IL-3 and stem cell factor into the co-culture. This cytokine-supplemented FT organ culture was used to examine the developmental capacity of individual hematopoietic progenitors in FL. Single cells of lineage marker (Lin) ‐ c-kit F Sca-1 F (Sca-1 F ) and Lin ‐ c-kit F Sca-1 ‐ (Sca-1 ‐ ) populations from the FL harvested at day 12 of gestation were cultured for 10 days, and the phenotypes of cells generated in each lobe were analyzed with a flow cytometer. All progenitors in the Sca-1 ‐ population were shown to be committed to generate only T, B or M cells. On the other hand, multipotent progenitors, which are capable of generating T, B and M cells, as well as unipotent progenitors committed to the T, B or M lineage were found in the Sca-1 F population. Bipotent progenitors generating M and T cells and those generating M and B cells were also found in the Sca-1 F population, which probably represent progenitors in the process of commitment. However, no bipotent progenitors generating T and B cells were detected.

Hemopoietic progenitors in the murine fetal liver capable of rapidly generating T cells.

Abstract: We investigated the hemopoietic progenitors in fetal liver (FL) compared with those in adult bone marrow (BM) for their ability to differentiate into T, B, and myeloid cells. Lineage marker-negative (Lin-) c-kit+ cells isolated from FL and BM were used as the source of progenitors. No apparent difference was observed between FL and BM progenitors in their ability to generate B and myeloid cells when these progenitors were cultured on a monolayer of a BM-derived stromal cell line. In marked contrast, FL progenitors were able to generate T cells much more rapidly than BM progenitors in both in vivo intrathymic cell transfer and fetal thymus organ culture systems. The same type of FL progenitors were also found in the FL of congenitally athymic nu/nu mice, indicating that these progenitors arise in FL independently of the fetal thymus. The present study have provided circumstantial evidence suggesting the presence of T cell lineage-committed progenitors in FL.