Heterogenic final cell cycle by chicken retinal Lim1 horizontal progenitor cells leads to heteroploid cells with a remaining replicated genome.

Heterogenic final cell cycle by chicken retinal Lim1 horizontal progenitor cells leads to heteroploid cells with a remaining replicated genome.
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DOI:
10.1371/journal.pone.0059133
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Hallböök F
Hallböök F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shirazi Fard S;Jarrin M;Boije H;Fillon V;All-Eriksson C;Hallböök F

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视网膜祖细胞在核迁移过程中发生顶端有丝分裂,新产生的有丝分裂后神经元迁移到其预期的视网膜层。尽管这对大多数类型的视网膜神经元是有效的,但鸡水平细胞是由专用祖细胞的延迟非顶端有丝分裂产生的。这种最终的细胞周期的调节还没有很好地理解,我们已经研究了Lim 1表达水平祖细胞(HPC)如何退出细胞周期。我们已经使用了S-和G2/M-期的标记物与细胞周期调节因子Rb 1,细胞周期蛋白B1,cdc 25 C和p27 Kip 1的标记物相结合,以确定HPC的最终细胞周期。结果表明,Lim 1 + HPC在何时以及在什么阶段离开最终细胞周期方面是异质的。并非所有的水平细胞都是由非顶端(基底)有丝分裂产生的;相反,HPC在最终的细胞周期中表现出三种不同的行为。据估计,35%的Lim 1+水平细胞由非顶端有丝分裂产生。其他水平细胞产生的一个interkinetic核迁移与顶端有丝分裂或由一个细胞周期与S期,随后没有任何有丝分裂。这样的细胞保留有复制的DNA,可以被认为是体细胞异倍体。在Rb 1、cyclin B1、cdc 25 C和p27 Kip 1的表达中也观察到最终细胞周期的异质性。磷酸化Rb 1-Ser 608仅限于进入S期的Lim 1+细胞,而cyclin B1和cdc 25 C仅在具有基础有丝分裂的HPC中表达。只有在顶端有丝分裂后离开细胞周期的HPC表达p27 Kip 1。我们推测,细胞周期的异质性与异倍体细胞的形成可能会提出一个细胞环境,有助于这些细胞产生癌症的倾向时,视网膜母细胞瘤基因突变的建议。
Retinal progenitor cells undergo apical mitoses during the process of interkinetic nuclear migration and newly generated post-mitotic neurons migrate to their prospective retinal layer. Whereas this is valid for most types of retinal neurons, chicken horizontal cells are generated by delayed non-apical mitoses from dedicated progenitors. The regulation of such final cell cycle is not well understood and we have studied how Lim1 expressing horizontal progenitor cells (HPCs) exit the cell cycle. We have used markers for S- and G2/M-phase in combination with markers for cell cycle regulators Rb1, cyclin B1, cdc25C and p27Kip1 to characterise the final cell cycle of HPCs. The results show that Lim1+ HPCs are heterogenic with regards to when and during what phase they leave the final cell cycle. Not all horizontal cells were generated by a non-apical (basal) mitosis; instead, the HPCs exhibited three different behaviours during the final cell cycle. Thirty-five percent of the Lim1+ horizontal cells was estimated to be generated by non-apical mitoses. The other horizontal cells were either generated by an interkinetic nuclear migration with an apical mitosis or by a cell cycle with an S-phase that was not followed by any mitosis. Such cells remain with replicated DNA and may be regarded as somatic heteroploids. The observed heterogeneity of the final cell cycle was also seen in the expression of Rb1, cyclin B1, cdc25C and p27Kip1. Phosphorylated Rb1-Ser608 was restricted to the Lim1+ cells that entered S-phase while cyclin B1 and cdc25C were exclusively expressed in HPCs having a basal mitosis. Only HPCs that leave the cell cycle after an apical mitosis expressed p27Kip1. We speculate that the cell cycle heterogeneity with formation of heteroploid cells may present a cellular context that contributes to the suggested propensity of these cells to generate cancer when the retinoblastoma gene is mutated.
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