LIF-dependent survival of embryonic stem cells is regulated by a novel palmitoylated Gab1 signalling protein.

The cytokine leukaemia inhibitory factor (LIF) promotes self-renewal of mouse embryonic stem cells (ESCs) through activation of the transcription factor Stat3. However, the contribution of other ancillary pathways stimulated by LIF in ESCs, such as the MAPK and PI3K pathways, is less well understood. We show here that naive-type mouse ESCs express high levels of a novel effector of the MAPK and PI3K pathways. This effector is an isoform of the Gab1 (Grb2-associated binder protein 1) adaptor protein that lacks the N-terminal pleckstrin homology (PH) membrane-binding domain. Although not essential for rapid unrestricted growth of ESCs under optimal conditions, the novel Gab1 variant (Gab1ß) is required for LIF-mediated cell survival under conditions of limited nutrient availability. This enhanced survival is absolutely dependent upon a latent palmitoylation site that targets Gab1ß directly to ESC membranes. These results show that constitutive association of Gab1 with membranes through a novel mechanism promotes LIF-dependent survival of murine ESCs in nutrient-poor conditions.

Stem cells and veterinary medicine: tools to understand diseases and enable tissue regeneration and drug discovery.

New sophisticated laboratory techniques, as well as established interactions between basic science, researchers and veterinarians, have led to an exponential increase in our understanding of the animal body in health and disease. The advent of animal cloning, the identification and characterization of stem cells, and publication of the various mammalian genomes has afforded the opportunity to exploit these technologies to better understand disease and develop new therapies. In human medicine, these medical advances are already being translated into clinical practice, the promise being that previously untreatable or incurable chronic diseases will become a thing of the past. In parallel, the veterinary profession is looking to these technologies to explore novel therapies for chronic diseases, such as osteoarthritis in companion animals, and is applying these technologies to enhance food animal production. This review focuses on the emerging area of stem cell biology and explores the potential applications of stem cell technologies to veterinary medicine.