A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cells

JE Till, EA McCulloch… - Proceedings of the …, 1964 - National Acad Sciences
JE Till, EA McCulloch, L Siminovitch
Proceedings of the National Academy of Sciences, 1964National Acad Sciences
FIG. 2.-Schematic outline of the spleen-colony progeny, a large majority of which technique.
are differentiated as judged by their morphology. Thus, the developmentof a colony involves
processes of differenti-ation occurring among the progeny from a single cell. Analysis of
thecell content ofthe resulting colony might be expected to cast light on any control
mechanisms which act during colony formation. If rigid control mechanisms are operative,
acting on cells of a relatively constant genotype, all colony-forming cells might be expected …
FIG. 2.-Schematic outline of the spleen-colony progeny, a large majority of which technique. are differentiated as judged by their morphology. Thus, the developmentof a colony involves processes of differenti-ation occurring among the progeny from a single cell. Analysis of thecell content ofthe resulting colony might be expected to cast light on any control mechanisms which act during colony formation. If rigid control mechanisms are operative, acting on cells of a relatively constant genotype, all colony-forming cells might be expected to behave in a similar fashion, and colony formation should be a relatively uniformprocess, giving rise to colonies with very similar characteristics. Alternatively, ifcontrol is lax, colonies with widely differing characteristics might be expected to develop. Results which may bear on this problem are available from experiments in which colonies were analyzed for their content of colony-forming cells. 8 It was found that, while most colonies contained these cells, their distribution among colonies was very heterogeneous, with many colonies containing few colony-forming cells, and a few containing very many. Thisresult suggests that control is lax. In the present paper, an analysis of this variation is presented which indicates that itmay be generated by a well-known probabilistic (" stochastic") process, the" birth-and-death" process. 9 Experimental Procedures.-The assay for colony-forming cells by the enumeration of spleen colonies has been published, 5and is represented diagrammatically inFigure 2. Inbrief, a cell suspension is prepared from adult mouse marrow, spleen, or
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