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研究揭示人类iPS细胞的细胞内组织和变化
2023-01-07 15:25

美国艾伦细胞科学研究所Susanne M. Rafelski课题组揭示人类iPS细胞的细胞内组织和变化。相关论文于2023年1月4日在线发表在《自然》杂志上。

研究人员表示,由于涉及大量的分子,它们的组合和它们决定的大量细胞行为,理解一个表达基因的子集如何决定细胞表型是一个相当大的挑战。
 
研究人员通过关注细胞的组织(细胞行为的关键读数和驱动因素),在代表不同细胞器和功能机器的主要细胞结构层面上降低了这种复杂性,并生成了WTC-11 hiPSC单细胞图像数据集v1,其中包含了超过20万个三维活细胞,横跨25个关键细胞结构。这个数据集的规模和质量能够创建出一个通用的分析框架,将细胞及其结构的原始图像数据转换为可由人类解释的降维、定量测量,并促进数据探索。这个框架包含了在正常人群中观察到的巨大的细胞间变异性,促进了逐个细胞结构数据的整合,并能够对不同细胞群内和不同细胞群间组织的不同、可分离方面进行定量分析。
 
研究人员发现,间期细胞的整合细胞内组织对群体中细胞形状的广泛变化是稳健的;一些结构的平均位置在集落边缘的细胞中变得极化,同时保持它们与其他结构相互作用的“线路”;相反,在早期有丝分裂重组期间,结构位置的变化伴随着它们线路的变化。
 
附:英文原文
 
Title: Integrated intracellular organization and its variations in human iPS cells

Author: Viana, Matheus P., Chen, Jianxu, Knijnenburg, Theo A., Vasan, Ritvik, Yan, Calysta, Arakaki, Joy E., Bailey, Matte, Berry, Ben, Borensztejn, Antoine, Brown, Eva M., Carlson, Sara, Cass, Julie A., Chaudhuri, Basudev, Cordes Metzler, Kimberly R., Coston, Mackenzie E., Crabtree, Zach J., Davidson, Steve, DeLizo, Colette M., Dhaka, Shailja, Dinh, Stephanie Q., Do, Thao P., Domingus, Justin, Donovan-Maiye, Rory M., Ferrante, Alexandra J., Foster, Tyler J., Frick, Christopher L., Fujioka, Griffin, Fuqua, Margaret A., Gehring, Jamie L., Gerbin, Kaytlyn A., Grancharova, Tanya, Gregor, Benjamin W., Harrylock, Lisa J., Haupt, Amanda, Hendershott, Melissa C., Hookway, Caroline, Horwitz, Alan R., Hughes, H. Christopher, Isaac, Eric J., Johnson, Gregory R., Kim, Brian, Leonard, Andrew N., Leung, Winnie W., Lucas, Jordan J., Ludmann, Susan A., Lyons, Blair M., Malik, Haseeb, McGregor, Ryan, Medrash, Gabe E., Meharry, Sean L., Mitcham, Kevin, Mueller, Irina A., Murphy-Stevens, Timothy L., Nath, Aditya, Nelson, Angelique M., Oluoch, Sandra A., Paleologu, Luana, Popiel, T. Alexander, Riel-Mehan, Megan M., Roberts, Brock, Schaefbauer, Lisa M., Schwarzl, Magdalena, Sherman, Jamie, Slaton, Sylvain, Sluzewski, M. Filip, Smith, Jacqueline E., Sul, Youngmee, Swain-Bowden, Madison J., Tang, W. Joyce, Thirstrup, Derek J., Toloudis, Daniel M., Tucker, Andrew P., Valencia, Veronica, Wiegraebe, Winfried, Wijeratna, Thushara

Issue&Volume: 2023-01-04

Abstract: Understanding how a subset of expressed genes dictates cellular phenotype is a considerable challenge owing to the large numbers of molecules involved, their combinatorics and the plethora of cellular behaviours that they determine1,2. Here we reduced this complexity by focusing on cellular organization—a key readout and driver of cell behaviour3,4—at the level of major cellular structures that represent distinct organelles and functional machines, and generated the WTC-11 hiPSC Single-Cell Image Dataset v1, which contains more than 200,000 live cells in 3D, spanning 25 key cellular structures. The scale and quality of this dataset permitted the creation of a generalizable analysis framework to convert raw image data of cells and their structures into dimensionally reduced, quantitative measurements that can be interpreted by humans, and to facilitate data exploration. This framework embraces the vast cell-to-cell variability that is observed within a normal population, facilitates the integration of cell-by-cell structural data and allows quantitative analyses of distinct, separable aspects of organization within and across different cell populations. We found that the integrated intracellular organization of interphase cells was robust to the wide range of variation in cell shape in the population; that the average locations of some structures became polarized in cells at the edges of colonies while maintaining the ‘wiring’ of their interactions with other structures; and that, by contrast, changes in the location of structures during early mitotic reorganization were accompanied by changes in their wiring.

DOI: 10.1038/s41586-022-05563-7

Source: https://www.nature.com/articles/s41586-022-05563-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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