Mechanisms responsible for size differences between hemopoietic colonies: an analysis using a CSF-dependent hemopoietic cell line.

Abstract

Cells of the colony stimulating factor (CSF)-dependent continuous hemopoietic cell line 32Dcl-3 generate strikingly different large, medium and small colonies in semisolid cultures. Reculture of cells from such colonies showed that all colony types contained clonogenic cells able again to form colonies of all three size types. Clone mapping showed that late initiation of colony formation did not account for the final size difference between colonies, a conclusion confirmed by mapping studies on normal CSF-stimulated murine granulocyte-macrophage colonies. Clonogenic cells within 32 D Clone 3 (32Dcl-3) colonies varied in quantitative responsiveness to CSF stimulation. This responsiveness was generally lower than that of the initiating clonogenic cell and was higher with cells from small colonies than with cells from corresponding large colonies. The data eliminated differences in intrinsic proliferative potential, cellular hierarchy, cell cycle times or responsiveness to CSF stimulation as an adequate explanation for colony size differences. Colony size differences may possibly arise from random differences in the sequence of self-generative versus differentiative divisions in clonogenic cells in developing clones.