Prochain séminaire MECABIONIC le 30/09/25

Our next MECABIONIC Seminar will be given by Raphaël Clément from the Institut de Biologie de Marseille on Tuesday, 30^th of September at 11am in the Meeting Room at the 5^th floor of the Fizeau building.

Cell fate decisions and self-organization in hierarchic tumors

Developmental tumors are often produced by the subversion of embryonic programs, in which stem cells fail to properly follow their differentiation trajectories. They are composed of cancer stem cells, which sustain tumor growth, and differentiated tumor cells, that eventually stop dividing. How cancer stem cells decide to either differentiate or self-renew is not known. Using simple developmental brain tumors in the Drosophila nervous system, we combined lineagetracing experiments to population dynamics modelling to determine the average, population-level self-renewal and differentiation probabilities of cancer stem cells, and show how they can lead to sustained growth and stable heterogeneity between cell types.

We next asked whether these probabilities are cell-intrinsic, and the same for all cancer stem cells, or if they depend on external signals from their environment. Implementing 3D tumor growth simulations, we found that cell-intrinsic differentiation probabilities cannot account for the spatial segregation of cell types observed in vivo. To assess the role cellular environment, we mapped differentiation events in 3D, and found that the differentiation probability is actually a direct, quantifiable function of the identity of surrounding cells. We finally turn to genetic pertubation experiments to uncover the maintenance/differentiation signalling pathways involved.

Taken together, our results show that fate decision in hierarchic tumors is determined by the µ-environment of cancer stem cells, and that such local decision rules can lead to self-organized spatial segregation and stable heterogeneity between cell types.