A stochastic model of self‐renewal and commitment to differentiation of the primitive hemopoietic stem cells in culture

We recently identified a murine hemopoietic stem cell colony which consists of undifferentiated (blast) cells and appears to be more primitive than CFU‐GEMM in the stem cell hierarchy. The progenitors for the colony which we termed “stem cell colony” possess an extensive self‐renewal capacity and the ability to generate many secondary multipotential hemopoietic colonies in culture. We replated a total of 68 stem cell colonies from cultures of murine spleen cells and analyzed the number of stem cell–and granulocyte(neutrophil)‐erythrocyte‐macrophage‐megakaryocyte (GEMM) colony‐forming cells in individual stem cell colonies. Of the 68 stem cell colonies, 35 contained progenitors (abbreviated as “S”‐cells) for stem cell colonies. The distributions of S‐cells and CFU‐GEMM in individual stem cell colonies were extremely heterogeneous. Neither the frequency distributions of S‐cells nor CFU‐GEMM in stem cell colonies could be fitted well by Poisson distribution. Rather, the frequency distribution of the s‐cells could be approximated by a geometric distribution and that of CFU‐GEMM by an exponential distribution, both of which are variates of the gamma distribution. Our observations are in agreement with those on the distributions of CFU‐S in individual spleen colonies and provided support for a stochastic model for stem cell self‐renewal and commitment in culture. Application of the theory of the branching process to the distribution of S‐cells revealed a distributional parameter “p” of 0.589 which is also in agreement with the earlier report on the p value for reproduction of CFU‐S.

[1]  Edward E. Gbur,et al.  Statistical modeling techniques , 1983 .

[2]  T. Nakahata,et al.  Clonal origin of murine hemopoietic colonies with apparent restriction to granuclocyte‐macrophage‐megakaryocyte (GMM) differentiation , 1982, Journal of cellular physiology.

[3]  T. Nakahata,et al.  Identification in culture of a class of hemopoietic colony-forming units with extensive capability to self-renew and generate multipotential hemopoietic colonies. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[4]  R. Humphries,et al.  Self-renewal of hemopoietic stem cells during mixed colony formation in vitro. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[5]  G. Johnson.  Colony formation in agar by adult bone marrow multipotential hemopoietic cells , 1980, Journal of cellular physiology.

[6]  C. Gilbert,et al.  Self‐maintenance capacity of CFU‐S , 1980, Journal of cellular physiology.

[7]  A. Fauser,et al.  Identification of megakaryocytes, macrophages, and eosinophils in colonies of human bone marrow containing neurtophilic granulocytes and erythroblasts , 1979 .

[8]  M. Ogawa,et al.  Murine hemopoietic colonies in culture containing normoblasts, macrophages, and megakaryocytes , 1978, American journal of hematology.

[9]  G. Johnson,et al.  Pure and mixed erythroid colony formation in vitro stimulated by spleen conditioned medium with no detectable erythropoietin. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[10]  N. Iscove,et al.  Partial replacement of serum by selenite, transferrin, albumin and lecithin in haemopoitec cell cultures , 1976, Nature.

[11]  J. Till,et al.  A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE GROWTH OF SPLEEN COLONY-FORMING CELLS. , 1964, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Till,et al.  A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. , 1961, Radiation research.

[13]  F. N. David,et al.  Principles and procedures of statistics. , 1961 .