Mapping Cell Cycle Plasticity with Spatial Proteomics

Mapping Cell Cycle Plasticity Across Human Cells, Tissues, and Organoids with Spatial Proteomics

ABSTRACT:

Cell cycle plasticity is a fundamental hallmark of every tumor, playing a crucial role in cancer initiation, progression, and treatment. We developed cell cycle mapping, a technological platform that combines highly multiplexed, single-cell imaging and machine learning to generate a “bird’s eye view” of the cell cycle, to reveal the plurality of paths cancer cells take through proliferative and arrested cell cycle state space, and the molecular mechanisms that govern this progression. Using the Cell DIVE multiplexed imaging platform, we obtain >100-plex imaging in human cell culture models and FFPE tissue microarray (TMA) libraries to investigate the contribution of cell cycle plasticity to tumor growth and drug resistance. We have profiled the cell cycle and tumor microenvironment (TME) landscape of >700 bladder tumors to investigate how differences in the spatial organization of bladder cancer histologies confer distinct proliferative phenotypes to tumors. We have also extended this multiplexed imaging approach into 3D patient-derived organoid (PDO) models co-cultured with match cancer-associated fibroblasts (CAFs), to study how interactions with specific CAF subtypes influences proliferative signature of pancreatic ductal adenocarcinoma (PDAC) tumors. 

The session will conclude with a live Q&A, giving audience the opportunity to engage directly with the presenters. In addition to providing an educational program, our goal is to raise awareness of, and encourage the adoption of, the spatial biology solutions we offer to the research community.

KEY LEARNINGS:

• Explore how Cell DIVE multiplexed imaging and machine learning create comprehensive maps of cell cycle plasticity at single-cell resolution.
• Understand how high-plex imaging can be extended from 2D tissues to 3D patient-derived organoid models to study tumor biology in physiologically relevant systems.
• Learn strategies for developing, validating, and scaling >100-marker imaging assays for robust, high-throughput translational and clinical research.

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