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

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
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培养中小鼠母细胞集落的增殖动力学和分化:早期多能造血祖细胞可变 G0 期和恒定倍增率的证据

DOI:
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发表时间:
1983
影响因子:
5.6
通讯作者:
M. Ogawa
M. Ogawa
中科院分区:
生物学2区
文献类型:
--
作者:
Tohio Suda;J. Suda;M. Ogawa

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一些研究者描述了在培养中表达多谱系分化的造血集落。我们最近鉴定了一类小鼠造血祖细胞,其形成具有非常高的再铺板效率的母细胞集落。为了进一步阐明培养中原始细胞集落祖细胞与多系造血集落祖细胞之间的关系,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。在从5-氟尿嘧啶(5-FU)处理小鼠获得的脾细胞培养物中,对母细胞集落发育为多谱系(和单谱系)集落的系列观察证实了小鼠母细胞集落的过渡性质。这些数据还表明,早期多能祖细胞在G 0期的时间是可变的,并且当触发进入细胞周期时,它们在分化的早期阶段以相对恒定的倍增率增殖。一些多能祖细胞处于G 0期的观点也得到了长期胸苷自杀研究的支持,在该研究中,脾细胞在培养物中暴露于高比活性的3 H-胸苷5天,洗涤,并测定存活的祖细胞。正常小鼠和5-FU处理小鼠第7天和第16天母细胞集落的再铺板能力比较表明,一些第7天母细胞集落来源于对5-FU敏感的成熟祖细胞群。相反,第16天原始细胞集落的祖细胞在细胞周期中处于休眠状态,不受5-FU处理的影响。以前我们报道过,第16天母细胞集落的祖细胞具有显著的自我更新能力。这些观察结果表明,自我更新的能力伴随着长时间的G 0,一旦分化发生,则发生活跃的细胞分裂。
Several investigators have described hemopoietic colonies expressing multilineage differentiation in culture. We recently identified a class of murine hemopoletic 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.