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培养条件下小鼠原始细胞集落的增殖动力学与分化:早期多能造血祖细胞存在可变G0期和恒定倍增率的证据

Proliferative kinetics and differentiation of murine blast cell colonies in culture: evidence for variable G0 periods and constant doubling rates of early pluripotent hemopoietic progenitors.

作者信息

Suda T, Suda J, Ogawa M

出版信息

J Cell Physiol. 1983 Dec;117(3):308-18. doi: 10.1002/jcp.1041170305.

DOI:10.1002/jcp.1041170305
PMID:6654987
Abstract

Several investigators have described hemopoietic colonies expressing multi-lineage differentiation in culture. We recently identified a class of murine hemopoietic progenitors which form blast cell colonies with very high replating efficiencies. In order to clarify further the relationship between progenitors for blast cell colonies and progenitors for the multilineage hemopoietic colonies in culture, we carried out analyses of kinetic and differentiation properties of murine blast cell colonies. Serial observations of the development of blast cell colonies into multilineage (and single lineage) colonies in cultures of spleen cells obtained from 5-fluorouracil (5-FU)-treated mice confirmed the transitional nature of the murine blast cell colonies. The data also suggested that the early pluripotent progenitors are in G0 for variable periods, and that when triggered into cell cycle, they proliferate at relatively constant doubling rates during the early stages of differentiation. The notion that some of the pluripotent progenitors are in G0 was also supported by long-term thymidine suicide studies in which spleen cells were exposed to 3H-thymidine with high specific activity for 5 days in culture, washed, and assayed for surviving progenitors. Comparison of replating abilities of day-7 and day-16 blast cell colonies from normal as well as 5-FU-treated mice indicated that some of the day-7 blast cell colonies are derived from maturer populations of progenitors which are sensitive to 5-FU. In contrast, progenitors for the day-16 blast cell colonies are dormant in cell cycle and were not affected by 5-FU treatment. Previously we reported that progenitors for day-16 blast cell colonies have a significant capacity for self-renewal. These observations suggest the hypothesis that the capability for self-renewal is accompanied by long periods of G0, and that once commitment to differentiation takes place, then active cell division occurs.

摘要

几位研究者描述了在培养中表达多谱系分化的造血集落。我们最近鉴定出一类小鼠造血祖细胞,它们能形成具有非常高再接种效率的原始细胞集落。为了进一步阐明培养中原始细胞集落的祖细胞与多谱系造血集落的祖细胞之间的关系,我们对小鼠原始细胞集落的动力学和分化特性进行了分析。对从5-氟尿嘧啶(5-FU)处理的小鼠获得的脾细胞培养物中原始细胞集落向多谱系(和单谱系)集落发育的连续观察,证实了小鼠原始细胞集落的过渡性质。数据还表明,早期多能祖细胞在G0期停留不同时间,并且当被触发进入细胞周期时,它们在分化早期以相对恒定的倍增速率增殖。长期的胸腺嘧啶核苷自杀研究也支持了一些多能祖细胞处于G0期的观点,在该研究中,脾细胞在培养中暴露于高比活性的3H-胸腺嘧啶核苷5天,洗涤后检测存活的祖细胞。对正常小鼠以及5-FU处理小鼠的第7天和第16天原始细胞集落再接种能力的比较表明,一些第7天的原始细胞集落源自对5-FU敏感的更成熟祖细胞群体。相反,第16天原始细胞集落的祖细胞处于细胞周期的休眠状态,不受5-FU处理的影响。我们之前报道过,第16天原始细胞集落的祖细胞具有显著的自我更新能力。这些观察结果提出了一个假说,即自我更新能力伴随着长时间的G0期,并且一旦发生向分化的定向,就会发生活跃的细胞分裂。

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Proliferative kinetics and differentiation of murine blast cell colonies in culture: evidence for variable G0 periods and constant doubling rates of early pluripotent hemopoietic progenitors.培养条件下小鼠原始细胞集落的增殖动力学与分化:早期多能造血祖细胞存在可变G0期和恒定倍增率的证据
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