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Multipotent and unipotent progenitors contribute to prostate postnatal development

Nature Cell Biology volume 14, pages 1131–1138 (2012)Cite this article

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Abstract

The prostate is a glandular epithelium composed of basal, luminal and neuroendocrine cells that originate from the urogenital sinus during embryonic development. After birth, the prostate keeps developing until the end of puberty. Here, we used inducible genetic lineage tracing experiments in mice to investigate the cellular hierarchy that governs prostate postnatal development. We found that prostate postnatal development is mediated by basal multipotent stem cells that differentiate into basal, luminal and neuroendocrine cells, as well as by unipotent basal and luminal progenitors. Clonal analysis of basal cells revealed the existence of bipotent and unipotent basal progenitors as well as basal cells already committed to the luminal lineage with intermediate cells co-expressing basal and luminal markers associated with this commitment step. The existence of multipotent basal progenitors during prostate postnatal development contrasts with the distinct pools of unipotent basal and luminal stem cells that mediate adult prostate regeneration. Our results uncover the cellular hierarchy acting during prostate development and will be instrumental in defining the cellular origin and the mechanisms underlying prostate cancer initiation.

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Figure 1: Basal cells give rise to basal, luminal and neuroendocrine cells during early postnatal development.
Figure 2: Basal cells give rise to basal, luminal and neuroendocrine cells during late postnatal development.
Figure 3: Multipotent and unipotent progenitors revealed by clonal analysis.
Figure 4: Intermediate cells and luminal differentiation of basal progenitors.
Figure 5: Unipotent luminal progenitors contribute to the luminal lineage expansion during early postnatal prostate development.
Figure 6: Unipotent luminal progenitors contribute to the luminal lineage expansion during late postnatal prostate development.
Figure 7: K18CREER/RosaYFP lineage tracing during late prostate postnatal development.
Figure 8: Model of the prostate cellular hierarchy during postnatal development, homeostasis and regeneration.

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Acknowledgements

We thank our colleagues who provided us with reagents, which are cited in the text. We thank our colleagues from the Blanpain laboratory and C. Govaerts for their comments on the manuscript and J-M. Vanderwinden and F. Bollet-Quivogne for their help with confocal imaging. C.B. and A.V.K. are chercheur qualifié, M.O. is a collaborateur scientifique of the FRS/FNRS. C.B. is an investigator of WELBIO. This work was supported by the FNRS, TELEVIE, the program d’excellence CIBLES of the Wallonia Region, a research grant from the Fondation Contre le Cancer, the ULB fondation, the fond Gaston Ithier, a starting grant of the European Research Council (ERC) and the EMBO Young Investigator Program.

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Author notes

  1. Marielle Ousset and Alexandra Van Keymeulen: These authors contributed equally to this work

Authors and Affiliations

  1. Université Libre de Bruxelles (ULB), IRIBHM, Brussels B-1070, Belgium

    Marielle Ousset, Alexandra Van Keymeulen, Gaëlle Bouvencourt, Neha Sharma & Cédric Blanpain

  2. Université Catholique de Louvain, de Duve Institute, Brussels B-1200, Belgium

    Younes Achouri

  3. Department of Physics, Cavendish Laboratory, J.J. Thomson Avenue, University of Cambridge, Cambridge CB3 0HE, United Kingdom

    Benjamin D. Simons

  4. The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, United Kingdom

    Benjamin D. Simons

  5. WELBIO, Brussels B-1070, Belgium

    Cédric Blanpain

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  1. Marielle Ousset
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Contributions

M.O., A.V.K. and C.B. designed the experiments and performed data analysis. M.O. and A.V.K. performed most of the experiments. B.D.S. performed mathematical modelling and data analysis. Y.A. generated K8CREER transgenic mice. G.B. and N.S. provided technical support. M.O. and A.V.K. prepared the figures. C.B. wrote the manuscript.

Corresponding authors

Correspondence to Marielle Ousset, Alexandra Van Keymeulen or Cédric Blanpain.

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The authors declare no competing financial interests.

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Ousset, M., Van Keymeulen, A., Bouvencourt, G. et al. Multipotent and unipotent progenitors contribute to prostate postnatal development. Nat Cell Biol 14, 1131–1138 (2012). https://doi.org/10.1038/ncb2600

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