Generation of a prostate from a single adult stem cell


The existence of prostate stem cells (PSCs) was first postulated from the observation that normal prostate regeneration can occur after repeated cycles of androgen deprivation and replacement in rodents1. Given the critical role of PSCs in maintaining prostate tissue integrity and their potential involvement in prostate tumorigenesis2, it is important to define specific markers for normal PSCs. Several cell-surface markers have been reported to identify candidate PSCs, including stem cell antigen-1 (Sca-1, also known as Ly6a), CD133 (Prom1) and CD44 (refs 3—10). However, many non-PSCs in the mouse prostate also express these markers and thus identification of a more defined PSC population remains elusive. Here we identify CD117 (c-kit, stem cell factor receptor) as a new marker of a rare adult mouse PSC population, and demonstrate that a single stem cell defined by the phenotype Lin-Sca-1+CD133+CD44+CD117+ can generate a prostate after transplantation in vivo. CD117 expression is predominantly localized to the region of the mouse prostate proximal to the urethra and is upregulated after castration-induced prostate involution—two characteristics consistent with that of a PSC marker. CD117+ PSCs can generate functional, secretion-producing prostates when transplanted in vivo. Moreover, CD117+ PSCs have long-term self-renewal capacity, as evidenced by serial isolation and transplantation in vivo. Our data establish that single cells in the adult mouse prostate with multipotent, self-renewal capacity are defined by a Lin-Sca-1+CD133+CD44+CD117+ phenotype.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: CD117 is preferentially expressed in the proximal region of the mouse prostate.
Figure 2: The CD117 + population enriches for normal adult prostate stem cells.
Figure 3: A single adult stem cell with the phenotype Lin - Sca-1 + CD133 + CD44 + CD117 + can generate a secretion-producing prostate.
Figure 4: Human prostates contain a subpopulation of CD117 + cells that localize to the basal layer of the prostate epithelium.


  1. 1

    Isaacs, J. T. in Control of Cell Proliferation and Cell Death in the Normal and Neoplastic Prostate. Benign Prostatic Hyperplasia (eds C. H. Rodgers et al.) Vol. II 85—94 (National Institutes of Health, Report No. 87—2881, 1987)

    Google Scholar 

  2. 2

    Abate-Shen, C. & Shen, M. M. Molecular genetics of prostate cancer. Genes Dev. 14, 2410—2434 (2000)

    CAS  Article  Google Scholar 

  3. 3

    Burger, P. E. et al. Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high capacity to reconstitute prostatic tissue. Proc. Natl Acad. Sci. USA 102, 7180—7185 (2005)

    ADS  CAS  Article  Google Scholar 

  4. 4

    Liu, A. Y. et al. Cell—cell interaction in prostate gene regulation and cytodifferentiation. Proc. Natl Acad. Sci. USA 94, 10705—10710 (1997)

    ADS  CAS  Article  Google Scholar 

  5. 5

    Richardson, G. D. et al. CD133, a novel marker for human prostatic epithelial stem cells. J. Cell Sci. 117, 3539—3545 (2004)

    CAS  Article  Google Scholar 

  6. 6

    Tsujimura, A. et al. Prostatic stem cell marker identified by cDNA microarray in mouse. J. Urol. 178, 686—691 (2007)

    CAS  Article  Google Scholar 

  7. 7

    Xin, L., Lawson, D. A. & Witte, O. N. The Sca-1 cell surface marker enriches for a prostate-regenerating cell subpopulation that can initiate prostate tumorigenesis. Proc. Natl Acad. Sci. USA 102, 6942—6947 (2005)

    ADS  CAS  Article  Google Scholar 

  8. 8

    Collins, A. T., Habib, F. K., Maitland, N. J. & Neal, D. E. Identification and isolation of human prostate epithelial stem cells based on α2β1-integrin expression. J. Cell Sci. 114, 3865—3872 (2001)

    CAS  PubMed  Google Scholar 

  9. 9

    Lawson, D. A., Xin, L., Lukacs, R. U., Cheng, D. & Witte, O. N. Isolation and functional characterization of murine prostate stem cells. Proc. Natl Acad. Sci. USA 104, 181—186 (2007)

    ADS  CAS  Article  Google Scholar 

  10. 10

    Schmelz, M. et al. Identification of a stem cell candidate in the normal human prostate gland. Eur. J. Cell Biol. 84, 341—354 (2005)

    CAS  Article  Google Scholar 

  11. 11

    Sugimura, Y., Cunha, G. R. & Donjacour, A. A. Morphogenesis of ductal networks in the mouse prostate. Biol. Reprod. 34, 961—971 (1986)

    CAS  Article  Google Scholar 

  12. 12

    Salm, S. N. et al. TGF-β maintains dormancy of prostatic stem cells in the proximal region of ducts. J. Cell Biol. 170, 81—90 (2005)

    CAS  Article  Google Scholar 

  13. 13

    Tsujimura, A. et al. Proximal location of mouse prostate epithelial stem cells: a model of prostatic homeostasis. J. Cell Biol. 157, 1257—1265 (2002)

    CAS  Article  Google Scholar 

  14. 14

    Wang, G. M., Kovalenko, B., Wilson, E. L. & Moscatelli, D. Vascular density is highest in the proximal region of the mouse prostate. Prostate 67, 968—975 (2007)

    Article  Google Scholar 

  15. 15

    Bonkhoff, H. & Remberger, K. Differentiation pathways and histogenetic aspects of normal and abnormal prostatic growth: a stem cell model. Prostate 28, 98—106 (1996)

    CAS  Article  Google Scholar 

  16. 16

    Signoretti, S. et al. p63 is a prostate basal cell marker and is required for prostate development. Am. J. Pathol. 157, 1769—1775 (2000)

    CAS  Article  Google Scholar 

  17. 17

    Cunha, G. R. & Lung, B. The possible influence of temporal factors in androgenic responsiveness of urogenital tissue recombinants from wild-type and androgen-insensitive (Tfm) mice. J. Exp. Zool. 205, 181—193 (1978)

    CAS  Article  Google Scholar 

  18. 18

    Xin, L., Ide, H., Kim, Y., Dubey, P. & Witte, O. N. In vivo regeneration of murine prostate from dissociated cell populations of postnatal epithelia and urogenital sinus mesenchyme. Proc. Natl Acad. Sci. USA 100, 11896—11903 (2003)

    ADS  CAS  Article  Google Scholar 

  19. 19

    Kurita, T., Medina, R. T., Mills, A. A. & Cunha, G. R. Role of p63 and basal cells in the prostate. Development 131, 4955—4964 (2004)

    CAS  Article  Google Scholar 

  20. 20

    Johnson, M. A., Hernandez, I., Wei, Y. & Greenberg, N. Isolation and characterization of mouse probasin: An androgen-regulated protein specifically expressed in the differentiated prostate. Prostate 43, 255—262 (2000)

    CAS  Article  Google Scholar 

  21. 21

    Shen, M. M. & Abate-Shen, C. Roles of the Nkx3. 1 homeobox gene in prostate organogenesis and carcinogenesis. Dev. Dyn. 228, 767—778 (2003)

    CAS  Article  Google Scholar 

  22. 22

    Weissman, I. L. Stem cells: units of development, units of regeneration, and units in evolution. Cell 100, 157—168 (2000)

    CAS  Article  Google Scholar 

  23. 23

    Lev, S., Blechman, J. M., Givol, D. & Yarden, Y. Steel factor and c-kit protooncogene: genetic lessons in signal transduction. Crit. Rev. Oncog. 5, 141—168 (1994)

    CAS  Article  Google Scholar 

  24. 24

    Ashman, L. K. The biology of stem cell factor and its receptor C-kit. Int. J. Biochem. Cell Biol. 31, 1037—1051 (1999)

    CAS  Article  Google Scholar 

  25. 25

    Perez-Losada, J. et al. Zinc-finger transcription factor Slug contributes to the function of the stem cell factor c-kit signaling pathway. Blood 100, 1274—1286 (2002)

    CAS  PubMed  Google Scholar 

  26. 26

    Moss, K. G., Toner, G. C., Cherrington, J. M., Mendel, D. B. & Laird, A. D. Hair depigmentation is a biological readout for pharmacological inhibition of KIT in mice and humans. J. Pharmacol. Exp. Ther. 307, 476—480 (2003)

    CAS  Article  Google Scholar 

  27. 27

    Heissig, B., Werb, Z., Rafii, S. & Hattori, K. Role of c-kit/Kit ligand signaling in regulating vasculogenesis. Thromb. Haemost. 90, 570—576 (2003)

    CAS  Article  Google Scholar 

  28. 28

    Shmelkov, S. V. et al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J. Clin. Invest. 118, 2111—2120 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Shackleton, M. et al. Generation of a functional mammary gland from a single stem cell. Nature 439, 84—88 (2006)

    ADS  CAS  Article  Google Scholar 

  30. 30

    Stingl, J. et al. Purification and unique properties of mammary epithelial stem cells. Nature 439, 993—997 (2006)

    ADS  CAS  Article  Google Scholar 

Download references


We thank J. Cupp, L. Gilmour and W. Tombo for FACS support, X.-D. Wang, R. Soriano and Z. Modrusan for microarray services, I. Kasman, L. Komuves and J. Eastham-Anderson for microscopy assistance, B. D. Tarlow for assistance with laser-capture microdissection and PCR-based genotyping, Genentech Laboratory Animal Resources for support services, L. Blocher and J. Simko for human clinical prostate specimens, and F. J. de Sauvage for valuable discussion, input and supervision of the project.

Author Contributions K.G.L. planned the project, designed and performed experiments, and prepared the manuscript. B.-E.W. assisted with ex vivo prostate studies. L.J. provided input and supervised the project. W.-Q.G. conceptualized the study, planned and supervised the project. All authors discussed the results and commented on the manuscript.

Author information



Corresponding author

Correspondence to Wei-Qiang Gao.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-14 with Legends (PDF 12718 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Leong, K., Wang, BE., Johnson, L. et al. Generation of a prostate from a single adult stem cell. Nature 456, 804–808 (2008).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing