Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration Journal Article


Authors: Peng, Y. C.; Levine, C. M.; Zahid, S.; Wilson, E. L.; Joyner, A. L.
Article Title: Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration
Abstract: The adult mouse prostate has a seemingly endless capacity for regeneration, and sonic hedgehog (SHH) signaling has been implicated in this stem cell-driven process. However, it is not clear whether SHH acts on the epithelium or stromal cells that secrete factors required for epithelial expansion. Because little is known about stromal stem cells compared with their epithelial counterparts, we used in vivo mouse genetics tools to characterize four prostate stromal subtypes and their stem cells. Using knockin reporter alleles, we uncovered that SHH signals from prostate basal epithelial cells to adjacent stromal cells. Furthermore, the SHH target gene Gli1 is preferentially expressed in subepithelial fibroblast-like cells, one of four prostate stromal subtypes and the subtype closest to the epithelial source of SHH. Using Genetic Inducible Fate Mapping to mark adult Gli1- or Smooth muscle actinexpressing cells and follow their fate during regeneration, we uncovered that Gli1-expressing cells exhibit long-term self-renewal capacity during multiple rounds of androgen-mediated regeneration after castration-induced involution, and depleted smooth muscle cells are mainly replenished by preexisting smooth muscle cells. Based on our Genetic Inducible Fate Mapping studies, we propose a model where SHH signals to multiple stromal stem cells, which are largely unipotent in vivo.
Keywords: controlled study; unclassified drug; androgen; nonhuman; animal cell; mouse; allele; animal tissue; gene targeting; smooth muscle fiber; gene expression; embryo; sonic hedgehog protein; animal experiment; animal model; gene frequency; cell fate; cell renewal; in vivo study; cell lineage; stem cell; gene mapping; prostate epithelium; fibroblast; epithelium cell; mesenchymal stem cell; cell regeneration; gene induction; homeostasis; stroma cell; transcription factor gli1; cell expansion; smooth muscle; intracellular signaling; smooth muscle actin; genetic fate mapping; male; priority journal; article; gli1 expression; mesenchymal lineage analysis; knockin
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 110
Issue: 51
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2013-12-17
Start Page: 20611
End Page: 20616
Language: English
DOI: 10.1073/pnas.1315729110
PROVIDER: scopus
PMCID: PMC3870668
PUBMED: 24218555
DOI/URL:
Notes: Cited By (since 1996):1 -- Export Date: 3 February 2014 -- CODEN: PNASA -- Source: Scopus
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MSK Authors
  1. Charles M Levine
    1 Levine
  2. Alexandra L Joyner
    83 Joyner
  3. Sarwar Zahid
    2 Zahid
  4. Yu-Ching   Peng
    5 Peng