s-SHIP expression identifies a subset of murine basal prostate cells as neonatal stem cells

// Guillaume Brocqueville 1 , Renee S. Chmelar 2 , Helene Bauderlique-Le Roy 1 , Emeric Deruy 3 , Lu Tian 1 , Robert L. Vessella 4 , Norman M. Greenberg 2, 5 , Larry R. Rohrschneider 2, * , Roland P. Bourette 1 1 University of Lille, CNRS, Institut Pasteur de Lille, UMR 8161-M3T-Mechanisms of Tumorigenesis and Targeted Therapies, SIRIC ONCOLille, F-59000 Lille, France 2 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA 3 BioImaging Center Lille, Institut Pasteur de Lille, University of Lille, F-59000 Lille, France 4 Department of Urology, University of Washington, Seattle, WA 98195, USA 5 Present address: NMG Scientific Consulting, North Potomac, MD 20878, USA * Deceased Correspondence to: Roland P. Bourette, e-mail: roland.bourette@ibl.cnrs.fr Keywords: stem cells, prostate, s-SHIP, epithelial cells, transgenic mouse Received: November 04, 2015      Accepted: March 28, 2016      Published: April 12, 2016 ABSTRACT Isolation of prostate stem cells (PSCs) is crucial for understanding their biology during normal development and tumorigenesis. In this aim, we used a transgenic mouse model expressing GFP from the stem cell-specific s-SHIP promoter to mark putative stem cells during postnatal prostate development. Here we show that cells identified by GFP expression are present transiently during early prostate development and localize to the basal cell layer of the epithelium. These prostate GFP + cells are a subpopulation of the Lin – CD24 + Sca-1 + CD49f + cells and are capable of self-renewal together with enhanced growth potential in sphere-forming assay in vitro , a phenotype consistent with that of a PSC population. Transplantation assays of prostate GFP + cells demonstrate reconstitution of prostate ducts containing both basal and luminal cells in renal grafts. Altogether, these results demonstrate that s-SHIP promoter expression is a new marker for neonatal basal prostate cells exhibiting stem cell properties that enables PSCs in situ identification and isolation via a single consistent parameter. Transcriptional profiling of these GFP + neonatal stem cells showed an increased expression of several components of the Wnt signaling pathway. It also identified stem cell regulators with potential applications for further analyses of normal and cancer stem cells.