Speaker
Description
Cancer cells exhibit a remarkable ability to adopt different phenotypic states in response to cell-intrinsic programs and environmental cues, a phenomenon known as cancer cell plasticity. Plasticity underlies tumour heterogeneity, treatment resistance, and metastasis. To move therapeutic approaches beyond pathway and enrichment analyses comparing early and late disease, we need to understand the principles governing the evolution of phenotypic composition and spatial organisation in cancerous tissue. Mechanistic modelling may be a great asset in this direction, allowing analysis of in vitro studies and in vivo spatial omics data from a complex systems perspective, linking local rules of cell division and state transition to emergent tissue-level patterns.
Here, I will present our work dissecting cell-intrinsic plasticity in colorectal cancer organoids. Perturbation experiments reveal ATRX, a chromatin remodelling enzyme, as a key regulator of plasticity. Using Markov-chain models, we leverage time-course cell sorting experiments to infer phenotypic transition networks following ATRX deletion and identify key transitions driving heterogeneity. I will discuss how to integrate these observations with in vivo spatial transcriptomics measurements, where plasticity is driven by environmental cues, and how analysing the spatial structure with complex systems methods further reveals tissue dynamics.
Bibliography
@article{cammareri2025loss,
title={Loss of colonic fidelity enables multilineage plasticity and metastasis},
author={Cammareri, Patrizia and Raponi, Michela and Hong, Yourae and Billard, Caroline V and Peckett, Nat and Zhu, Yujia and Velez-Bravo, Fausto D and Younger, Nicholas T and Dunican, Donnchadh S and Pohl, Sebastian {\"O}-G and others},
journal={Nature},
volume={644},
number={8076},
pages={547--556},
year={2025},
publisher={Nature Publishing Group UK London}
}
