No. 12

Title: Defining origins and progression of human colorectal cancer from spatial profiling

Speaker: Ken S. Lau

                Professor

                Department of Cell and Developmental Biology

               Vanderbilt University

Host：Xu Tan

           Chinese Institutes for Medical Research, Beijing

Time：15:00-16:30, Nov. 28, 2023 (Tuesday)

Location: Room 1322, North Tower, Basic Research Building, Capital Medical University 

Abstract：

Recent genome-scale profiling approaches have transformed our understanding of tissue biology, especially within human specimens. Here, we will discuss results from our efforts in generating a human colorectal precancer multi-omic atlas, and the accompanying insights into colorectal tumor initiation and progression. Single-cell transcriptomic and imaging analyses of the two most common human colorectal precancers, conventional adenomas and serrated polyps revealed that adenomas originate from WNT-driven stem cell expansion, while serrated polyps develop through gastric metaplasia. Cytotoxic immune infiltration is independent of tumor mutation burden at the precancer stage, and the stem and metaplasia dichotomy, as well as their accompanying immune microenvironments, translate into cancer counterparts. In another effort, spatial multi-omic data generated from colorectal specimens unveiled personalized clonal evolutionary dynamics and corresponding microenvironment alterations. Notably, an Immune Exclusion signature associated with progression of tumor regions with chromosomal instability (CIN+), influencing cytotoxic cell infiltration and offering prognostic value. These multi-omic atlases enhance our understanding of tumor progression, enabling precision surveillance and potential targeted interventions.

Selected Papers:

1. Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps. Cell, 2021, 184(26):6262-6280
2. Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors. bioRxiv, 2023.03.09.530832 (Cell, accepted)