Nucleoli and the nucleoli-centromere association are dynamic during normal development and in cancer.
Nucleoli and the nucleoli-centromere association are dynamic during normal development and in cancer.
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DOI：
10.1091/mbc.e22-06-0237
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发表时间：
2023-04-01
影响因子：
3.3
通讯作者：
Huang, Sui
中科院分区：
文献类型：
--
作者：
Rodrigues, Aaron;MacQuarrie, Kyle L.;Freeman, Emma;Lin, Alicia;Willis, Alexander B.;Xu, Zhaofa;Alvarez, Angel A.;Ma, Yongchao;White, Bethany E. Perez;Foltz, Daniel R.;Huang, Sui
在果蝇和哺乳动物细胞中，着丝粒聚集在核仁周围，但核仁-着丝粒相互作用的意义仍有待研究。为了确定在不同的生理和病理条件下的相互作用是否是动态的，我们研究了核仁结构和着丝粒在不同的分化阶段，使用细胞培养模型和结果显示动态变化的核仁特征和核仁-着丝粒的相互作用，通过分化和癌细胞。胚胎干细胞通常具有单个大核仁，其与高百分比的着丝粒成簇。当细胞分化为中间状态时，核仁数目增加，着丝粒结合减少。在终末分化的细胞中，包括肌管、神经元和角质形成细胞，核仁的数量及其与着丝粒的结合是最低的。癌细胞表现出核仁数目和核仁-着丝粒关联的模式，这类似于增殖细胞类型，表明核仁重组和核仁-着丝粒相互作用的变化可能在促进恶性转化中起作用。这一观点在一例儿童横纹肌肉瘤中得到了支持，在该病例中诱导分化减少了核仁数目和着丝粒结合。这些发现表明，在正常发育和癌症中，核仁结构在着丝粒功能和对细胞功能至关重要的基因组组织中起着积极的作用。
Centromeres are known to cluster around nucleoli in Drosophila and mammalian cells, but the significance of the nucleoli–centromere interaction remains underexplored. To determine whether the interaction is dynamic under different physiological and pathological conditions, we examined nucleolar structure and centromeres at various differentiation stages using cell culture models and the results showed dynamic changes in nucleolar characteristics and nucleoli–centromere interactions through differentiation and in cancer cells. Embryonic stem cells usually have a single large nucleolus, which is clustered with a high percentage of centromeres. As cells differentiate into intermediate states, the nucleolar number increases and the centromere association decreases. In terminally differentiated cells, including myotubes, neurons, and keratinocytes, the number of nucleoli and their association with centromeres are at the lowest. Cancer cells demonstrate the pattern of nucleoli number and nucleoli–centromere association that is akin to proliferative cell types, suggesting that nucleolar reorganization and changes in nucleoli–centromere interactions may play a role in facilitating malignant transformation. This idea is supported in a case of pediatric rhabdomyosarcoma, in which induced differentiation reduces the nucleolar number and centromere association. These findings suggest active roles of nucleolar structure in centromere function and genome organization critical for cellular function in both normal development and cancer.
影响因子：
3.7
作者：
Chen CC;Greene E;Bowers SR;Mellone BG
通讯作者：
Mellone BG