Stem cells are generally thought to maintain homeostasis in adult tissues, producing committed progenitor cells that in turn generate terminal differentiated cells. Although adult stem cells have been studied intensively, far less is known about how they function in vivo to maintain tissue homeostasis. It has long been assumed that adult tissues are maintained by long lived, slow cycling, self renewing stem cells which generate a population of committed progenitors known as “transit amplifying” (TA) cells. TA cells undergo several rounds of proliferation, after which they terminally differentiate. This widely accepted model has been called into question by a recent study of the epidermis, which shows that the normal tissue is maintained by a single type of progenitor cell capable of both asymmetric and symmetric cell division, stem cells being quiescent under normal conditions. It is unclear whether this single compartment model will apply to other tissues as well as the epidermis. In this project we will study how tissue homeostasis is achieved in another stratified squamous epithelium, that of the oesophagus. By defining the behaviour of a representative sample of progenitor cells, we will be able to determine whether their behaviour conforms to the predictions of the stem and TA cell hypothesis or an alternative model. Since many of the pathways that control normal stem cell fate have been associated to tumour development, advances in the knowledge of the oesophageal homeostasis will establish the basis for further research in the study of the molecular alterations that lead to cancer development in this little studied but important tissue, which is a common cause of human disease.
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