Speaker: Hu Zheng, Ph.D., Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences

Time: 10:00-11:30 a.m., Nov 21, 2024, GMT+8

Venue: Room B117, Research Complex #2, PKU 

Abstract: 

Unravelling the origin and evolution of precancerous lesions is crucial for effectively preventing malignant transformation, yet our knowledge remains limited. Here we used a base editor-enabled DNA barcoding system to comprehensively map single-cell phylogenies in mouse models of intestinal tumorigenesis induced by inflammation or loss of the Ape gene. Through quantitative analysis of high-resolution phylogenies including 260,922 single cells from normal, inflamed and neoplastic intestinal tissues, we identified tens of independent cell lineages undergoing parallel clonal expansions within each lesion. We also found polyclonal origins of human sporadic colorectal polyps through bulk exome sequencing and single-gland whole-genome sequencing. Genomic and clinical data support a model of polyclonal-to-monoclonal transition, with monoclonality representing a more advanced stage. Single-cell RNA-seq revealed extensive intercellular interactions in early polyclonal lesions, but there was significant loss of interactions during monoclonal transition. Therefore, our data suggest that colorectal precancer is often founded by many different lineages and highlight their cooperative interactions. These findings provide insights into opportunities for earlier intervention in colorectal cancer.

Source: Biomedical Pioneering Innovation Center, PKU