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Causes and Consequences of Plasticity in Cancer and Development

Dana Pe'er, Memorial Sloan Kettering Cancer Center
Tuesday November 9, 12-1pm
Zoom Link:聽

Abstract:聽Cellular plasticity, the ability to take on unexpected fates or identities, is a fundamental property of multicellular life that enables coordination during development and wound healing. A number of diseases lead to greatly enhanced plasticity, with cancer perhaps foremost among these. We show how high-resolution single-cell approaches such as transcriptome and chromatin accessibility profiling can be exploited to understand the causes and consequences of cellular plasticity. Using analytical approaches that we developed to identify cellular trajectories and cell-state transitions and to quantify cell fate potential from this data, we reveal striking plasticity in the context of early endodermal development in the mouse. We describe a number of approaches for quantifying plasticity, and demonstrate how both oncogenic mutation and environmental insults can lead to dramatic increases in tumor cell plasticity. Our work provides insights into putative regulatory mechanisms underlying these phenotypic expansions, and reveals how cancer cells can inappropriately gain access to diverse developmental programs that allow them to colonize new anatomical sites during metastasis. Over and over, we observe that cancer cells use developmental plasticity as an adaptive mechanism for dealing with new environments and driving malignant progression.