The potential impact of stem cells in various biomedical fields is enormous. A pilot project was therefore set up to explore the nature and fate of stem or progenitor cells in different contexts. Such knowledge will be useful for devising cell-based replacement therapies to treat diseases resulting from inappropriate or massive cell death. It will also help to unravel the mechanisms of tumour cell spreading.

We are exploring novel approaches in stem cell research using different model systems. One of the projects focuses on the development of the central nervous system in mice, in particular the study of the “hedgehog” signalling pathway in neural stem cells. This molecular chain of events, which plays a key role in regulating brain organogenesis, is also involved in promoting tumour growth. The team leading this project has formerly succeeded in blocking the development of human brain cancers transplanted in mice, by targeting the resident stem cells.

The role of stem cells in the endocrine pancreas is a matter of major interest. Diabetes results from the inappropriate death of pancreatic insulin-producing cells (ß-cells), and their regeneration constitutes a considerable challenge. In one of the studies, the fate of progenitors will be followed during pancreas formation to determine the potential of individual cells in terms of proliferation, differentiation and response to environmental signals. The aim of the second study derives from an astonishing observation made with a transgenic mouse model of inducible diabetes. Adult animals can indeed spontaneously recover from this disease after the initiation of massive ß-cell loss, by regenerating up to 20% of the initial cell mass. We are therefore trying to identify cell progenitors responsible for this regeneration.

Insulin is part of a family of growth factors that modulate many physiological activities. We are examining their role in regulating spermatogonial stem cell renewal and spermatogenesis in mice. Although these factors are known to be essential for male reproductive function, their precise roles remain elusive. Transgenic mice lacking receptors for those factors on specific cell lineages are being developed as a tool of investigation.

Stem cells and cell plasticity are also explored with the hydra as a model. This polyp, which spontaneously regenerates after amputation, is useful to investigate the role of apoptosis (programmed cell death) on the behaviour of progenitors and stem cells in regenerative context. We propose to identify the signals released by the apoptotic cells that trigger proliferation of stem cells in specific regions of the animal. Deciphering this complex cellular interaction is important in view of the fact that apoptosis is also a common response to injury in humans.