Modelling stem cell behavior during planarian regeneration

Regrowing functional body parts after amputation remains a distant dream for humans, but it seems a mere trifle for many flatworm species. For regeneration, stem cells must travel distances of centimetres to reach the wound site. So how do they find their way? And how do they interact to orchestrate migration, cell division and differentiation?

Flatworms can regenerate every body part, including the brain, even from tiny amputation fragments corresponding to only a fraction of the original body size. The highly abundant stem cells are vital players during regeneration, which gives rise to all newly forming tissues. These cells are only a few micrometres in diameter but travel distances of centimetres to reach the wound site.

The researchers of this project combine in-situ fluorescence measurements with novel techniques of stem cell manipulation, physics-inspired data analysis approaches and computational modelling to understand stem cell behaviour during planarian regeneration. For example, they use cell elongation as a read-out for the migration direction and a theoretical framework developed for LCDs to characterize migration-induced cell alignment. Preliminary data already reveals a rich repertoire of behaviours depending on the type of amputation and the position of the stem cell in the body.

Progress (September 2022)

So far, the researchers could only base their analysis on 2D sections, and a class of stem cell-derived progenitor cells. To extend their work to the complete set of migrating cells and, most notably, the more densely packed stem cells themselves, they are developing image processing techniques to reliably segment cells and extract their shape in 3D. They also devise a modelling framework based on cellular Potts models to simulate stem cell behaviour and thus test their experimentally obtained hypotheses.