Integrated intracellular organization and its variations in human iPS cells
Authors: 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 , Yang Ruian , Zaunbrecher Rebecca J. , Labitigan Ramon Lorenzo D. , Sanborn Adrian L. , Johnson Graham T. , Gunawardane Ruwanthi N. , Gaudreault Nathalie , Theriot Julie A. , Rafelski Susanne M. 
Published: January 2023

AbstractUnderstanding 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.