Cell differentiation lineage in the prostate

Prostatic epithelium consists mainly of luminal and basal cells, which are presumed to differentiate from common progenitor/stem cells. We hypothesize that progenitor/stem cells are highly concentrated in the embryonic urogen ital sinus epithelium from which prostatic epithelial buds develop. We furt her hypothesize that these epithelial progenitor/stem cells are also presen t within the basal compartment of adult prostatic epithelium and that the s pectrum of differentiation markers of embryonic and adult progenitor/stem c ells will be similar. The present study demonstrates that the majority of c ells in embryonic urogenital sinus epithelium and developing prostatic epit helium (rat, mouse, and human) coexpressed luminal cytokeratins 8 and 18 (C K8, CK18), the basal cell cytokeratins (CK14, CK5), p63, and the so-called transitional or intermediate cell markers, cytokeratin 19 (CK19) and glutat hione-S-transferase-pi (GSTpi). The majority of luminal cells in adult rode nt and human prostates only expressed luminal markers (CK8, CK18), while th e basal epithelial cell compartment contained several distinct subpopulatio ns. In the adult prostate, the predominant basal epithelial subpopulation e xpressed the classical basal cell markers (CK5, CK14, p63) as well as CK19 and GSTpi. However, a small fraction of adult prostatic basal epithelial ce lls co-expressed the full spectrum of basal and luminal epithelial cell mar kers (CK5, CK14, CK8, CK18, CK19, p63, GSTpi). This adult prostatic basal e pithelial cell subpopulation, thus, exhibited a cell differentiation marker profile similar to that expressed in embryonic urogenital sinus epithelium . These rare adult prostatic basal epithelial cells are proposed to be the progenitor/stem cell population. Thus, we propose that at all stages (embryonic to adult) prostatic epitheli al progenitor/stem cells maintain a differentiation marker profile similar to that of the original embryonic progenitor of the prostate, namely urogen ital sinus epithelium. Adult progenitor/stem cells co-express both luminal cell, basal cell, and intermediate cell markers. These progenitor/stem cell s differentiate into mature luminal cells by maintaining CK8 and CK18, and losing all other makers. Progenitor/stem cells also give rise to mature bas al cells by maintaining CK5, CK14, p63, CK19, and GSTpi and losing K8 and K 18. Thus, adult prostate basal and luminal cells are proposed to be derived from a common pleuripotent progenitor/stem cell in the basal compartment t hat maintains its embryonic profile of differentiation markers from embryon ic to adult stages.