Self-Renewal and Multilineage Differentiation In Vitro from Murine Prostate Stem Cells
Article first published online: 19 JUL 2007
Copyright © 2007 AlphaMed Press
Volume 25, Issue 11, pages 2760–2769, November 2007
How to Cite
Xin, L., Lukacs, R. U., Lawson, D. A., Cheng, D. and Witte, O. N. (2007), Self-Renewal and Multilineage Differentiation In Vitro from Murine Prostate Stem Cells. STEM CELLS, 25: 2760–2769. doi: 10.1634/stemcells.2007-0355
- Issue published online: 2 JAN 2009
- Article first published online: 19 JUL 2007
- Manuscript Accepted: 9 JUL 2007
- Manuscript Received: 9 MAY 2007
- Prostate sphere assay;
- Androgen receptor;
- Integrin α6;
- Prostate stem cell antigen
Murine prostate stem cells express integrin α6, which modulates survival, proliferation, and differentiation signaling through its interaction with the extracellular protein laminin. When plated in vitro in laminin containing Matrigel medium, 1 of 500–1,000 murine prostate cells can grow and form clonogenic spheroid structures that we term prostate spheres. Prostate spheres can be serially passaged individually or in bulk to generate daughter spheres with similar composition, demonstrating that sphere-forming cells are capable of self-renewal. Spheres spontaneously undergo lineage specification for basal and transit-amplifying cell types. P63-expressing cells localized to the outer layers of prostate spheres possess higher self-renewal capacity, whereas cells toward the center display a more differentiated transit-amplifying phenotype, as demonstrated by the expression of the prostate stem cell antigen. When dihydrotestosterone is added to the medium, the androgen receptor is stabilized, is imported to the nucleus, and drives differentiation to a luminal cell-like phenotype. A fraction of sphere cells returned to an in vivo environment can undergo differentiation and morphogenesis to form prostate tubular structures with defined basal and luminal layers accompanied by prostatic secretions. This study demonstrates self-renewal and multilineage differentiation from single adult prostate stem/progenitor cells in a specific in vitro microenvironment.
Disclosure of potential conflicts of interest is found at the end of this article.