Spacial associations of centromeres in the nuclei of hematopoietic cells: evidence for cell-type-specific organizational patterns
Spacial associations of centromeres in the nuclei of hematopoietic cells: evidence for cell-type-specific organizational patterns
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DOI：
10.1182/blood.v95.5.1608.005k32_1608_1615
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发表时间：
2000-03-01
期刊：
影响因子：
20.3
通讯作者：
Parreira, L
中科院分区：
文献类型：
--
作者：
Alcobia, I;Dilao, R;Parreira, L
据信，着丝粒异染色质在间期的三维组织可能作为调控基因表达的表观遗传机制具有功能相关性。因此，一个可能的可能性是，在细胞周期的G1期观察到的异染色质结构（染色中心）中空间结合的着丝粒在不同的细胞中会有所不同。我们试图解决这个问题，作为一个模型，在静止的正常人造血细胞和原代成纤维细胞中观察到的染色中心。要做到这一点，我们分析了空间关系的3-D保存细胞使用非同位素原位杂交和共聚焦显微镜。我们定量地表明，所有细胞类型中的染色中心确实代表了某些着丝粒的非随机空间关联。此外，观察到的着丝粒联合模式表明，这些细胞类型中的染色中心由特定着丝粒的不同组合组成，造血细胞与成纤维细胞在它们的染色中心的组成方面有显著的不同，外周血细胞中的着丝粒似乎聚集成不同的“髓样”细胞，（存在于单核细胞和粒细胞中）和“淋巴样”（存在于淋巴细胞中）空间模式。这些发现支持这样的想法，即在静止的造血细胞的细胞核中形成的染色中心可能代表异染色质的细胞类型特异性基因表达的调控参与核隔室，进一步表明，着丝粒异染色质在间期的空间排列在造血分化过程中个体发育决定。(C)2000年，美国血液学会。
It is believed that the 3-dimensional organization of centromeric heterochromatin in interphase may be of functional relevance as an epigenetic mechanism for the regulation of gene expression. Accordingly, a likely possibility is that the centromeres that spatially associate into the heterochromatic structures (chromocenters) observed in the G1 phase of the cell cycle will differ in different cells. We sought to address this issue using, as a model, the chromocenters observed in quiescent normal human hematopoietic cells and primary fibroblasts. To do this, we analyzed the spatial relationships 3-D preserved cells using nonisotopic in situ hybridization and confocal microscopy. We showed quantitatively that chromocenters in ail cell types do indeed represent nonrandom spatial associations of certain centromeres. Furthermore, the observed patterns of centromere association indicate that the chromocenters in these cell types are made of different combinations of specific centromeres, that hematopoietic cells are strikingly different from fibroblasts as to the composition of their chromocenters and that centromeres in peripheral blood cells appear to aggregate into distinct "myeloid" (present in monocytes and granulocytes) and "lymphoid" (present in lymphocytes) spatial patterns. These findings support the idea that the chromocenters formed in the nucleus of quiescent hematopoietic cells might represent heterochromatic nuclear compartments involved in the regulation of cell-type-specific gene expression, further suggesting that the spatial arrangement of centromeric heterochromatin in interphase is ontogenically determined during hematopoietic differentiation. (C) 2000 by The American Society of Hematology.