DESCRIPTION:

This presentation will highlight how recording cellular life histories using multimodal lineage tracing approaches provides new insight into colorectal cancer initiation, progression, and therapeutic resistance. By integrating genetic, transcriptional, and evolutionary information at single-cell resolution, these approaches enable reconstruction of clonal dynamics from normal to cancer. I will emphasize key differences between mouse and human intestinal biology, underscoring the need for human-relevant model systems to accurately study tumor evolution and tissue regeneration (IBD). I will further discuss how quiescent stem cell states act as an evolutionary safeguard against tumorigenesis, while also serving as a reservoir for tumor persistence and therapeutic resistance. Finally, I will explore how tissue-specific constraints and adaption shape cancer susceptibility.

LEARNING OBJECTIVES:

• Understand how lineage tracing and multimodal single-cell approaches can be used to reconstruct clonal evolution in colorectal cancer.
• Recognize the role of quiescent stem states in tissue regeneration and their contribution to therapeutic resistance.
• Emphasize key biological differences between mouse and human intestine and their implications for modeling intestinal pathophysiology.