title: Cell kinetic studies fail to identify sequentially proliferating progenitors as the major source of epithelial renewal in the adult murine prostate.
abstract: There is evidence that stem cells and their progeny play a role in the development of the prostate. Although stem cells are also considered to give rise to differentiated progeny in the adult prostate epithelium ex vivo, the cohort of adult prostate stem cells in vivo as well as the mechanisms by which the adult prostate epithelium is maintained and regenerated remain highly controversial. We have attempted to resolve this conundrum by performing in vivo tracing of serially replicating cells after the sequential administration of two thymidine analogues to mice. Our results show that, during normal prostate homeostasis, sequentially proliferating cells are detected at a rate that is consistent with a stochastic process. These findings indicate that in vivo, under steady-state conditions, most adult prostate epithelial cells do not represent the progeny of a small number of specialized progenitors that generate sequentially replicating transit-amplifying (TA) cells but are formed by stochastic cell division. Similarly, no rapidly cycling TA cells were detected during regeneration following one cycle of androgen-mediated involution/regeneration of the prostate epithelium. These findings greatly enhance our understanding of the mechanisms regulating prostate epithelial cell renewal and may have significant implications in defining the cell of origin of proliferative prostatic diseases.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Pignon
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Chiara
authors.initials: C
authors.lastname: Grisanzio
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Carvo
authors.affiliation: Harvard Medical School, Boston, Massachusetts, United States of America; Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Lillian
authors.initials: L
authors.lastname: Werner
authors.affiliation: Harvard Medical School, Boston, Massachusetts, United States of America; Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Meredith
authors.initials: M
authors.lastname: Regan
authors.affiliation: Departments of Cell Biology and Urology, School of Medicine, New York University, New York, New York, United States of America.
authors.forename: E Lynette
authors.initials: EL
authors.lastname: Wilson
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism; D008297:Male; D051379:Mice; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism