Human fetal/tumor metakaryotic stem cells: pangenomic homologous pairing and telomeric end-joining of chromatids

Amanda N. Gruhl , Elena V. Gostjeva , William G. Thilly , Janna N. Fomina , Firouz Darroudi
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引用次数: 8

Abstract

Metakaryotic cells and syncytia with large, hollow, bell-shaped nuclei demonstrate symmetrical and asymmetrical amitotic nuclear fissions in microanatomical positions and numbers expected of stem cell lineages in tissues of all three primordial germ layers and their derived tumors. Using fluorescence in situ hybridization, mononuclear metakaryotic interphase cells have been found with only 23 centromeric and 23 telomeric staining regions. Syncytial bell-shaped nuclei found approximately during weeks 5–12 of human gestation display 23 centromeric and either 23 or 46 telomeric staining regions. These images suggest that (1) homologous chromatids pair at centromeres and telomeres, (2) all paired telomeres join end-to-end with other paired telomeres in all mononuclear and some syncytial metakaryotic cells, and (3) telomere junctions may open and close during the syncytial phase of development. Twenty-three telomeric joining figures could be accounted by 23 rings of one chromatid pair each, a single pangenomic ring of 23 joined chromatid pairs, or any of many possible sets of oligo-chromatid pair rings. As telomeric end-joining may affect peri-telomeric gene expression, a programmed sequence of telomeric end-joining associations in metakaryotic stem cells could guide developmental arboration and errors in, or interruptions of, this program could contribute to carcinogenesis.

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人胎儿/肿瘤元核干细胞:全基因组同源配对和染色单体端粒末端连接
具有大、中空、钟形细胞核的后核分裂细胞和合胞体在显微解剖位置和数量上显示对称和不对称的无丝分裂核分裂,这是所有三个原始生殖层及其衍生肿瘤组织中干细胞谱系的预期。利用荧光原位杂交技术,发现单核间期细胞只有23个着丝粒和23个端粒染色区。大约在人类妊娠5-12周发现的合胞钟形核显示23个着丝粒和23或46个端粒染色区。这些图像表明:(1)在着丝粒和端粒处同源染色单体成对;(2)在所有单核细胞和一些合胞性元核细胞中,所有配对的端粒端到端连接;(3)在合胞发育阶段,端粒连接可能打开和关闭。23个端粒连接数可以由每个染色单体对的23个环,一个由23个染色单体对连接的单全基因组环,或许多可能的少染色单体对环中的任何一组来解释。由于端粒末端连接可能影响周围端粒基因的表达,元核干细胞中端粒末端连接关联的程序化序列可能引导发育流产,而该程序的错误或中断可能导致癌变。
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