The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems

Abstract

The precise relationship between the stem cells for the lymphoid system and those for the blood-forming system is unclear. While it is generally assumed that the hemopoietic stem cell, the spleen colony-forming unit (CFU-S), is also the stem cell for the lymphoid system, there is little evidence for this hypothesis. To investigate the stem cells in these two systems, we irradiated bone marrow cells to induce unique chromosome aberrations in the stem cell population and injected them at limiting dilution into stem cell-deficient recipients. Several months (between 3 and 11) were allowed for the injected cells to repopulate the hemopoietic system. At that time, the bone marrow, spleen, and thymus were examined for a high frequency of cells having the same unique chromosome aberration. The presence of such markers shows that the marker was induced in a cell with extensive proliferative capacity, i.e., a stem cell. In addition, the splenic lymphocytes were stimulated with phytohemagglutinin (PHA) or lipopolysaccharide (LPS) to search for unique chromosomes in dividing T and B cells, respectively. Finally, bone marrow cells were injected into secondary irradiated recipients to determine if the marker occurred in CFU-S and to determine whether or not the same tissue distributions of marked cells could be propogated by bone marrow cells in a second recipient. After examination of 28 primary recipients, it was possible to identify three unique patterns of stem cell regeneration. In one set of mice, a unique chromosome marker was observed in CFU-S and in PHA- and LPS-stimulated cultures. These mice provide direct evidence for a pluripotent stem cell in bone marrow. In addition, two restricted stem cells were identified by this analysis. In three recipients, abnormal karyotypes were found only in myeloid cells and not in B and T lymphocytes. These mice presumably received a marked stem cell restricted to differentiate only into myeloid progeny. In three other recipients, chromosome aberrations were found only in PHA-stimulated cells; CFU-S and cells from LPS cultures did not have cells with the unique chromosome. This pattern suggests that bone marrow contains cells committed to differentiation only into T lymphocytes. For each of the three types of stem cells, secondary recipients had the same cellular distribution of marked cells as the primary recipients. This observation provides further evidence that unique markers can be induced in both pluripotent and restricted stem cells.

Committed T lymphocyte stem cells of rats. Characterization by surface W3/13 antigen and radiosensitivity.

“…There would be prima facie evidence for such committed stem cells, able to yield only one or other type of lymphocyte, if procedures were found that differentially replenish the mature B and T compartments of repopulated irradiated hosts. Abramson et al (2) induced chromosome markers by irradiation and followed the progeny of uniquely marked individual stem cells. They found signs of a committed T stem cell in bone marrow.…”

“…T and B lymphocytes are descended from a common ancestor, a muhipotent stem cell (1,2). The question arises as to the stage at which these two lineages diverge.…”

Integrative molecular and developmental biology of adult stem cells

“…In the mouse model, transplantation of total bone marrow cells has been known for almost 30 years to fully repopulate both the lymphoid and myeloid lineages of conditioned recipients (Abramson et al, 1977). A major advance in the field of HSC biology was the extensive characterization of the phenotype of murine HSCs.…”

Identification of a novel population of human cord blood cells with hematopoietic and chondrocytic potential

“…Human hematopoietic stem cells (HSCs) have been identified in bone marrow (BM), peripheral blood and umbilical cord blood (CB) [1][2][3][4]. Initially, the functional capacity of the cells derived from these tissues was believed to be restricted to a hematopoietic cell fate.…”