Modelling stem cell behaviour during planarian regeneration

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 characterise 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. The researchers also discovered that a cancer drug can be used for reversible arrest of stem cells in the cell cycle. Such protocols for experiments and analyses are important tools to study stem cell behaviour.

A cornerstone of the project is the development of computational tools to model the migration of single cells or a group of cells in response to chemical stimuli. Cell migration is important for many physiological and pathological processes, for example during embryonic development to form a complex body, during wound healing and regeneration, yet also during cancer metastasis. The cell’s ability to sense the external signals and to polarise in the direction of the signal is a primary step in the cell migration process, which can be simulated via the framework of Cellular Potts models (CPM).

The project will yield a well-documented repository of cell-based models of cell sensing, polarisation and migration using an open-source cell-based Cellular Potts model software (Compucell3D). The research especially explores the fundamental properties and complex intricacies of the CPM framework, which are often overlooked.

Progress (August 2023)

Since the project has yielded tools for quantifying cell migration and for manipulating stem cells, the work is currently focusing on the development of a computational framework to model cell migration. For example, together with their collaborator at the University of Utrecht (Kirsten ten Tusscher), the researchers document little-known details and pitfalls when setting up CPM simulations. Furthermore, a plan is developed to incorporate the CPM framework in courses at the WUR and UU and to train students in this useful modelling technique.