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一种体外培养的原始造血干细胞自我更新和分化定向的随机模型。

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

作者信息

Nakahata T, Gross A J, Ogawa M

出版信息

J Cell Physiol. 1982 Dec;113(3):455-8. doi: 10.1002/jcp.1041130314.

DOI:10.1002/jcp.1041130314
PMID:7174743
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.

摘要

我们最近鉴定出一种小鼠造血干细胞集落,它由未分化(原始)细胞组成,在干细胞层级结构中似乎比CFU - GEMM更原始。我们将这种集落的祖细胞称为“干细胞集落”,它们具有广泛的自我更新能力以及在培养中产生许多次级多能造血集落的能力。我们从鼠脾细胞培养物中总共传代培养了68个干细胞集落,并分析了各个干细胞集落中干细胞以及粒细胞(中性粒细胞) - 红细胞 - 巨噬细胞 - 巨核细胞(GEMM)集落形成细胞的数量。在这68个干细胞集落中,有35个含有干细胞集落的祖细胞(简称为“S”细胞)。各个干细胞集落中S细胞和CFU - GEMM的分布极其不均一。干细胞集落中S细胞和CFU - GEMM的频率分布均不能很好地用泊松分布拟合。相反,S细胞的频率分布可用几何分布近似,CFU - GEMM的频率分布可用指数分布近似,这两种分布都是伽马分布的变量。我们的观察结果与关于单个脾集落中CFU - S分布的观察结果一致,并为培养中干细胞自我更新和定向分化的随机模型提供了支持。将分支过程理论应用于S细胞的分布,得出分布参数“p”为0.589,这也与早期关于CFU - S增殖的p值报告一致。

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