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.
Highlights
Most tissues contain a small dedicated stem cell population, which is essential for maintaining tissue homeostasis and for tissue repair after injury [1, 2]
We investigated s-SHIP/green fluorescent protein (GFP) expression in neonatal and adult prostate of Tg 11.5kb-GFP mice and we showed that s-SHIP/GFPexpressing prostatic epithelial cells represent a subset of neonatal basal epithelial cell population with stem cell properties
At that time, branching morphogenesis is almost entirely complete, suggesting that s-SHIP/GFP-expressing cells may contribute to the early formation of the prostate cellular architecture
Summary
Most tissues contain a small dedicated stem cell population, which is essential for maintaining tissue homeostasis and for tissue repair after injury [1, 2]. We investigated s-SHIP/GFP expression in neonatal and adult prostate of Tg 11.5kb-GFP mice and we showed that s-SHIP/GFPexpressing prostatic epithelial cells represent a subset of neonatal basal epithelial cell population with stem cell properties These cells localize to the basal region during ductal canalization, exhibiting a Lin− CD24+ Sca-1+ CD49f+ basal phenotype, are enriched for prostate sphereforming activity in vitro, and can regenerate prostatic tubules in vivo. These results demonstrate that s-SHIP promoter expression offers a valuable marker of stem cell populations for both mammary and prostate tissues
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