1. Integrated intracellular organization and its variations in human iPS cells.
- Author
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Viana MP, Chen J, Knijnenburg TA, Vasan R, Yan C, Arakaki JE, Bailey M, Berry B, Borensztejn A, Brown EM, Carlson S, Cass JA, Chaudhuri B, Cordes Metzler KR, Coston ME, Crabtree ZJ, Davidson S, DeLizo CM, Dhaka S, Dinh SQ, Do TP, Domingus J, Donovan-Maiye RM, Ferrante AJ, Foster TJ, Frick CL, Fujioka G, Fuqua MA, Gehring JL, Gerbin KA, Grancharova T, Gregor BW, Harrylock LJ, Haupt A, Hendershott MC, Hookway C, Horwitz AR, Hughes HC, Isaac EJ, Johnson GR, Kim B, Leonard AN, Leung WW, Lucas JJ, Ludmann SA, Lyons BM, Malik H, McGregor R, Medrash GE, Meharry SL, Mitcham K, Mueller IA, Murphy-Stevens TL, Nath A, Nelson AM, Oluoch SA, Paleologu L, Popiel TA, Riel-Mehan MM, Roberts B, Schaefbauer LM, Schwarzl M, Sherman J, Slaton S, Sluzewski MF, Smith JE, Sul Y, Swain-Bowden MJ, Tang WJ, Thirstrup DJ, Toloudis DM, Tucker AP, Valencia V, Wiegraebe W, Wijeratna T, Yang R, Zaunbrecher RJ, Labitigan RLD, Sanborn AL, Johnson GT, Gunawardane RN, Gaudreault N, Theriot JA, and Rafelski SM
- Subjects
- Humans, Single-Cell Analysis, Datasets as Topic, Interphase, Cell Shape, Mitosis, Cell Polarity, Cell Survival, Induced Pluripotent Stem Cells cytology, Intracellular Space
- 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 determine
1,2 . 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., (© 2023. The Author(s).)- Published
- 2023
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