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SBME invited guest lecture: Dr. Ru Gunawardane (Allen Institute)
March 9 @ 9:00 am - 10:00 am
Dr. Ru Gunawardane (Executive Director | Allen Institute for Cell Science)
Creating and image-based map of cell states from pluripotency through differentiation
Overview: The Allen Institute for Cell Science aims to understand the principles by which human induced pluripotent stem cells (hiPSCs) establish and maintain robust dynamic localization of cellular structures and how they transition between states during differentiation and disease. Towards this aim, we created a collection of fluorescent-tagged clonal hiPSC lines (Allen Cell Collection) using CRISPR/Cas9 to fluorescently tag proteins that localize to the major organelles of the cell and various computational tools for analysis and integration of our large-scale data. Live cell imaging, image analysis, modeling and visualization, and open distribution to the scientific community define our endeavor. To date we have generated fluorescently tagged hiPSC clonal lines for ~50 major cellular structures and performed key genetic, cell biological, and stem cell validation. We have used these cell lines, along with various computational tools to generate image-based integrated models of cell organization and dynamics in hiPSCs to create a baseline of “normal” cell states. Using these tools, we are working on understanding the epithelial organization of the undifferentiated hiPS cells, dynamics of major organelles during cell division and early mesoderm differentiation, and the organization of the sarcomere in hiPSC-derived cardiomyocytes. In addition, we are integrating data modalities through imaging to better understand the relationship between cell organization and gene expression during differentiation. This approach integrates quantitative image-based readouts of gene expression, transcript localization, and cellular organization co-measured in single cells and leads to a better understanding of cell behaviors and cell states. Our cell lines, plasmids, 3D images, various analysis and visualization tools, integrated cell models, and biological findings are available to the research community.