Computationally enhanced quantitative phase microscopy reveals autonomous oscillations in mammalian cell growth.
Computationally enhanced quantitative phase microscopy reveals autonomous oscillations in mammalian cell growth.
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DOI：
10.1073/pnas.2002152117
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发表时间：
2020-11-03
影响因子：
11.1
通讯作者：
Kirschner MW
中科院分区：
文献类型：
--
作者：
Liu X;Oh S;Peshkin L;Kirschner MW
在细胞生长研究中，细胞团是线性增长还是指数增长一直是一个长期存在的问题。这两个模型意味着根本不同的机制，和歧视的两个需要特殊的测量精度。在这里，我们开发了一种方法，计算增强的定量相位显微镜，这大大提高了在贴壁哺乳动物细胞的单细胞生长测量的准确性和吞吐量。对几种细胞系的研究表明，单个细胞的生长动力学不能用任何一种简单的传统模型来解释;相反，它们呈现出一种意想不到的和显著的振荡行为，表明生长、细胞分裂和大小的调节和反馈更为复杂。生长和分裂的微妙平衡是细胞生理学的基本特性，也是人们最不了解的特性之一。它的研究一直受到精确测量细胞大小的困难以及测量单个细胞随时间的生长的更大挑战的阻碍。我们解决这些限制，展示了一个计算增强的方法，定量相显微镜贴壁细胞，使用改进的图像处理算法和自动化的细胞跟踪软件。准确性提高了两倍以上，这种改进足以建立细胞生长的动力学和遵守简单的生长规律。它也足以揭示细胞生长的未知特征，以前无法测量。随着这些方法和分析的改进，在几个细胞系中，我们记录了生长速率的显着振荡，发生在整个细胞周期中，与细胞分裂或出生偶联，但不依赖于细胞周期的进展。我们希望，进一步探索这种先进的工具将提供更好地了解哺乳动物细胞的生长速率调节。
It has been a long-standing question in cell growth studies whether the mass of cells grows linearly or exponentially. The two models imply fundamentally distinct mechanisms, and discrimination of the two requires exceptional measurement accuracy. Here, we develop a method, computationally enhanced quantitative phase microscopy, which greatly improves the accuracy and throughput for single-cell growth measurements in adherent mammalian cells. Studies in several cell lines indicate that the growth dynamics of individual cells cannot be explained by either of the simple conventional models; rather, they present an unanticipated and remarkable oscillatory behavior, suggesting more complex regulation and feedbacks in growth, cell division, and size. The fine balance of growth and division is a fundamental property of the physiology of cells, and one of the least understood. Its study has been thwarted by difficulties in the accurate measurement of cell size and the even greater challenges of measuring growth of a single cell over time. We address these limitations by demonstrating a computationally enhanced methodology for quantitative phase microscopy for adherent cells, using improved image processing algorithms and automated cell-tracking software. Accuracy has been improved more than twofold and this improvement is sufficient to establish the dynamics of cell growth and adherence to simple growth laws. It is also sufficient to reveal unknown features of cell growth, previously unmeasurable. With these methodological and analytical improvements, in several cell lines we document a remarkable oscillation in growth rate, occurring throughout the cell cycle, coupled to cell division or birth yet independent of cell cycle progression. We expect that further exploration with this advanced tool will provide a better understanding of growth rate regulation in mammalian cells.
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影响因子：
48
作者：
Godin, Michel;Delgado, Francisco Feijo;Son, Sungmin;Grover, William H.;Bryan, Andrea K.;Tzur, Amit;Jorgensen, Paul;Payer, Kris;Grossman, Alan D.;Kirschner, Marc W.;Manalis, Scott R.
通讯作者：
Manalis, Scott R.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1007/978-1-61779-182-6_6
发表时间：
2011-01-01
期刊：
CELL CYCLE SYNCHRONIZATION: METHODS AND PROTOCOLS
影响因子：
--
作者：
Darzynkiewicz, Zbigniew;Halicka, H. Dorota;Podhorecka, Monika
通讯作者：
Podhorecka, Monika
哺乳动物细胞和酵母细胞协调细胞生长和细胞周期进展的方式的差异。
影响因子：
--
作者：
Conlon, Ian;Raff, Martin
通讯作者：
Raff, Martin
影响因子：
16.6
作者：
Cadart C;Monnier S;Grilli J;Sáez PJ;Srivastava N;Attia R;Terriac E;Baum B;Cosentino-Lagomarsino M;Piel M
通讯作者：
Piel M