Decoding Cellular Phenotypes: A Dive into Cellular Organization with Dr. Susanne Rafelski

In this episode, we welcome Dr. Susanne Rafelski, a leading expert in cellular organization, to explore the complex interplay between gene expression and cellular phenotype. The challenge of understanding how a subset of expressed genes influences cellular phenotype is daunting due to the sheer number of involved molecules, their combinations, and the multitude of cellular behaviors they determine.Dr. Rafelski's research reduces this complexity by focusing on cellular organization—a critical determinant and indicator of cell behavior. She introduces the WTC-11 hiPSC Single-Cell Image Dataset v1, a remarkable dataset containing over 200,000 live 3D cells across 25 key cellular structures. The scale and quality of this dataset have allowed for the creation of a comprehensive analysis framework to convert raw image data into dimensionally reduced, human-interpretable, quantitative measurements, promoting data exploration.Dr. Rafelski talks us through how this framework harnesses the vast cell-to-cell variability seen within a normal population, integrates cell-by-cell structural data, and supports quantitative analyses of distinct aspects of organization within and across cell populations. Her team found that the integrated intracellular organization of interphase cells remained robust amidst the wide range of variation in cell shape in the population. Furthermore, the average locations of some structures became polarized in cells at the colony edges while maintaining their 'wiring' with other structures. Join us as we delve into the fascinating world of cellular organization and discover how changes in structure location during early mitotic reorganization are accompanied by changes in their wiring.Key Words: Cellular Organization, Gene Expression, Cellular Phenotype, WTC-11 hiPSC Single-Cell Image Dataset v1, Data Analysis Framework, Cell Variability, Structural Data, Mitotic Reorganization.Viana, M.P., Chen, J., Knijnenburg, T.A. et al. Integrated intracellular organization and its variations in human iPS cells. Nature 613, 345–354 (2023). https://doi.org/10.1038/s41586-022-05563-7 Slides: https://docs.google.com/presentation/d/1VO2SUjtnPV-6GvXboP1Uap1G2hKtSux0PEUoQwT7760/edit#slide=id.p1