1. Department of Developmental Biology and
2. Department of Genetics, Stanford University School of Medicine, Stanford, California 94305-5329 , USA
3. Department of Zoology, University of Oxford, Oxford OX1 3PS, UK

Correspondence to: Margaret T. Fuller^1,3 Correspondence and requests for materials should be addressed to M.F. (e-mail: Email: fuller@cmgm.stanford.edu).

Abstract

Stem cells maintain populations of highly differentiated, short-lived cell-types, including blood, skin and sperm, throughout adult life¹. Understanding the mechanisms that regulate stem cell behaviour is crucial for realizing their potential in regenerative medicine². A fundamental characteristic of stem cells is their capacity for asymmetric division: daughter cells either retain stem cell identity or initiate differentiation. However, stem cells are also capable of symmetric division where both daughters remain stem cells^{3, 4, 5, 6}, indicating that mechanisms must exist to balance self-renewal capacity with differentiation. Here we present evidence that support cells surrounding the stem cells restrict self-renewal and control stem cell number by ensuring asymmetric division. Loss of function of the Drosophila Epidermal growth factor receptor in somatic cells disrupted the balance of self-renewal versus differentiation in the male germline, increasing the number of germline stem cells. We propose that activation of this receptor specifies normal behaviour of somatic support cells; in turn, the somatic cells play a guardian role, providing information that prevents self-renewal of stem cell identity by the germ cell they enclose.