Nuclear DNA methylation and chromatin condensation phenotypes are distinct between normally proliferating/aging, rapidly growing/immortal, and senescent cells.
Nuclear DNA methylation and chromatin condensation phenotypes are distinct between normally proliferating/aging, rapidly growing/immortal, and senescent cells.
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DOI：
10.18632/oncotarget.942
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发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
Tajbakhsh J
中科院分区：
文献类型：
--
作者：
Oh JH;Gertych A;Tajbakhsh J
本研究报告探讨了原位染色质纹理特征（例如核 DNA 甲基化和染色质浓缩模式）在评估增殖能力（即细胞的生长行为）中的实用性，通过荧光染色可视化并通过专用三维 (3D) 定量和高通量逐个细胞图像分析进行评估：提供细胞群的更动态的图像，对基础科学、癌症诊断/预后和治疗药物开发具有潜在影响。对两种类型的原代细胞和四种不同的癌细胞系进行增殖，并在培养的不同点进行细胞计数、流式细胞术、共聚焦成像和 3D 图像分析。此外，一部分原代细胞和癌细胞因氧化应激而加速衰老。当原代细胞在培养物中老化时，DNA甲基化和染色质浓缩水平随着倍增时间的缩短而降低，在增殖衰老阶段达到最低水平。相比之下，具有恒定但较高倍增时间的永生癌细胞大多表现出较低且恒定水平的两种原位衍生特征。然而，与达到自然生长停滞的原代细胞相比，应激诱导的衰老原代细胞和癌细胞表现出相似水平的这些特征。就整体 DNA 甲基化和染色质浓缩水平而言，快速生长的癌细胞似乎处于正常增殖细胞和衰老细胞之间的中间水平。因此，正常细胞显然在衰老过程中的某个时刻达到了与癌细胞相当的两个参数阶段，这可能挑战这两种类型细胞之间的表型区别。伴随的高分辨率分子分析可以提供有关可能的潜在差异的信息，从而解释良性与恶性细胞的生长行为。
This study reports on probing the utility of in situ chromatin texture features such as nuclear DNA methylation and chromatin condensation patterns — visualized by fluorescent staining and evaluated by dedicated three-dimensional (3D) quantitative and high-throughput cell-by-cell image analysis — in assessing the proliferative capacity, i.e. growth behavior of cells: to provide a more dynamic picture of a cell population with potential implications in basic science, cancer diagnostics/prognostics and therapeutic drug development. Two types of primary cells and four different cancer cell lines were propagated and subjected to cell-counting, flow cytometry, confocal imaging, and 3D image analysis at various points in culture. Additionally a subset of primary and cancer cells was accelerated into senescence by oxidative stress. DNA methylation and chromatin condensation levels decreased with declining doubling times when primary cells aged in culture with the lowest levels reached at the stage of proliferative senescence. In comparison, immortal cancer cells with constant but higher doubling times mostly displayed lower and constant levels of the two in situ-derived features. However, stress-induced senescent primary and cancer cells showed similar levels of these features compared with primary cells that had reached natural growth arrest. With regards to global DNA methylation and chromatin condensation levels, aggressively growing cancer cells seem to take an intermediate level between normally proliferating and senescent cells. Thus, normal cells apparently reach cancer-cell equivalent stages of the two parameters at some point in aging, which might challenge phenotypic distinction between these two types of cells. Companion high-resolution molecular profiling could provide information on possible underlying differences that would explain benign versus malign cell growth behaviors.
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影响因子：
4
作者：
Campisi, Judith
通讯作者：
Campisi, Judith
DOI：
10.18632/aging.100023
发表时间：
2009-02-13
期刊：
Aging
影响因子：
--
作者：
Dimauro T;David G
通讯作者：
David G
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
5.3
作者：
Araujo, FD;Knox, JD;Zannis-Hadjopoulos, M
通讯作者：
Zannis-Hadjopoulos, M
影响因子：
18.2
作者：
Campisi J
通讯作者：
Campisi J