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

✍ Scribed by Tatsutoshi Nakahata; Alan J. Gross; Makio Ogawa

• Publisher: John Wiley and Sons
• Year: 1982
• Tongue: English
• Weight: 476 KB
• Volume: 113
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041130314

✦ Synopsis

Abstract

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.