Characterization of adult prostatic progenitor/stem cells exhibiting self-renewal and multilineage differentiation.
Demonstration of the hallmarks of stem cells, self-renewal and multilineage differentiation, is a challenge that has not been met for numerous tissues postulated to possess adult stem cells, including prostate tissue. Using a defined medium, we reproducibly isolated and maintained adult mouse prostatic cells with characteristics of progenitor/stem cells. Clonal populations of cells demonstrated tissue-specific multilineage differentiation by their ability to generate organized prostatic ductal structures in vivo, with luminal and basal cell layers, when grafted under the renal capsules of mice in the presence of fetal rat urogenital mesenchyme. Complete differentiation was demonstrated by the expression and secretion of terminally differentiated prostatic secretory products into the lumens. Self-renewal was demonstrated by serial transplantation of clonal populations that generated fully differentiated ductal structures in vivo. In vitro, undifferentiated cells expressed markers associated with prostate stem cells, including Sca 1 and CD49f, as well as basal cell markers (p63 and cytokeratins 5 and 14) and, at a low level, luminal cell markers (androgen receptor and cytokeratins 8 and 18). When grafted and allowed to differentiate in the presence of fetal urogenital mesenchyme, the cells differentiated into luminal cells and basal cells with more restricted protein expression patterns. These studies are the first to report a reproducible system to assess adult prostatic progenitor/stem cells.
Barclay
Wendy W
WW
Department of Cancer Biology, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Axanova
Linara S
LS
Chen
Wenhong
W
Romero
Lina
L
Maund
Sophia L
SL
Soker
Shay
S
Lees
Cynthia J
CJ
Cramer
Scott D
SD
D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D039503:Integrin alpha6 / Q000378:metabolism; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011467:Prostate / Q000166:cytology*; D051381:Rats; D011995:Recombination, Genetic / Q000235:genetics; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*
C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; C000593751:Atxn1 protein, rat; D015415:Biomarkers; D039503:Integrin alpha6; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins