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Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries

Nature volume 428, pages 564–569 (2004)Cite this article

Abstract

Many tissues including blood, skin, gut and germ cells are continuously maintained by tissue stem cells1,2. Under certain conditions, however, other organs can undergo repair using stem-cell-like progenitors generated by cell de-differentiation3. Cell fates have been broadened experimentally4,5,6,7, but mechanisms allowing de-differentiation to a stem cell state are poorly known. Germline stem cells begin to differentiate by forming interconnected germ cell cysts (cystocytes), and under certain conditions male mouse cystocytes have been postulated to revert into functional progenitors8,9. Here we report that four- and eight-cell Drosophila germline cystocytes generated either in second instar larval ovaries or in adults over-producing the BMP4-like stem cell signal Decapentaplegic efficiently convert into single stem-like cells. These de-differentiated cells can develop into functional germline stem cells and support normal fertility. Our results show that cystocytes represent a relatively abundant source of regenerative precursors that might help replenish germ cells after depletion by genotoxic chemicals, radiation or normal ageing. More generally, Drosophila cystocytes now provide a system for studying de-differentiation and its potential as a source of functional stem cells.

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Figure 1: Adult ovariole and L2 larval ovary.
Figure 2: Germ cell cysts in L2 larval ovaries revert to single cells.
Figure 3: Reverting cystocytes close ring canals and become functional GSCs.
Figure 4: GSC reversion in adult flies.

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References

  1. Spradling, A. C., Drummond-Barbosa, D. & Kai, T. Stem cells find their niche. Nature 414, 98–104 (2001)

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Watt, F. M. & Hogan, B. L. M. Out of Eden: stem cells and their niches. Science 287, 1427–1430 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Stocum, D. L. Amphibian regeneration and stem cells. Curr. Top. Microbiol. Immunol. 280, 1–70 (2000)

    Google Scholar 

  4. Mikkola, I., Heavey, B., Horcher, M. & Busslinger, M. Reversion of B cell commitment upon loss of Pax5 expression. Science 297, 110–113 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Morrison, S. J. et al. Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. Cell 101, 499–510 (2000)

    Article  CAS  PubMed  Google Scholar 

  6. Prohaska, S. S., Scherer, D. C., Weissman, I. L. & Kondo, M. Developmental plasticity of lymphoid progenitors. Semin. Immunol. 14, 377–384 (2002)

    Article  CAS  PubMed  Google Scholar 

  7. Pearson, B. J. & Doe, C. Q. Regulation of neuroblast competence in Drosophila. Nature 425, 624–628 (2003)

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Clermont, Y. & Bustos-Obregon, E. Re-examination of spermatogonial renewal in the rat by means of seminiferous tubules mounted ‘in toto’. Am. J. Anat. 122, 237–247 (1968)

    Article  CAS  PubMed  Google Scholar 

  9. De Rooij, D. G. & Russell, L. D. All you wanted to know about spermatogonia but were afraid to ask. J. Androl. 21, 776–798 (2000)

    Article  CAS  PubMed  Google Scholar 

  10. Song, X., Zhu, C. H., Doan, C. & Xie, T. Germline stem cells anchored by adherens junctions in the Drosophila ovary niches. Science 296, 1855–1857 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Xie, T. & Spradling, A. C. decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary. Cell 94, 251–260 (1998)

    Article  CAS  PubMed  Google Scholar 

  12. Chen, D. & McKearin, D. Dpp signaling silences bam transcription directly to establish asymmetric divisions of germline stem cells. Curr. Biol. 13, 1786–1791 (2003)

    Article  CAS  PubMed  Google Scholar 

  13. de Cuevas, M., Lilly, M. A. & Spradling, A. C. Germline cyst formation in Drosophila. Annu. Rev. Genet. 31, 405–428 (1997)

    Article  CAS  PubMed  Google Scholar 

  14. de Cuevas, M. & Spradling, A. C. Morphogenesis of the Drosophila fusome and its implications for oocyte specification. Development 125, 2781–2789 (1998)

    Article  CAS  PubMed  Google Scholar 

  15. Kai, T. & Spradling, A. C. An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells. Proc. Natl Acad. Sci. USA 100, 4633–4638 (2003)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhu, C. H. & Xie, T. Clonal expansion of stem cells during niche formation in Drosophila. Development 130, 2579–2588 (2003)

    Article  CAS  PubMed  Google Scholar 

  17. Ohlstein, B. & McKearin, D. Ectopic expression of the Drosophila Bam protein eliminates oogenic germline stem cells. Development 124, 3651–3662 (1997)

    Article  CAS  PubMed  Google Scholar 

  18. Godt, D. & Laski, F. A. Mechanisms of cell rearrangement and cell recruitment in Drosophila ovary morphogenesis and the requirement of bric-a-brac. Development 121, 173–187 (1995)

    Article  CAS  PubMed  Google Scholar 

  19. Robinson, D. N., Cant, K. & Cooley, L. Morphogenesis of Drosophila ovarian ring canals. Development 120, 2015–2025 (1994)

    Article  CAS  PubMed  Google Scholar 

  20. Dodson, G. S., Guarnieri, D. J. & Simon, M. A. Src64 is required for ovarian ring canal morphogenesis during Drosophila oogenesis. Development 125, 2883–2892 (1998)

    Article  CAS  PubMed  Google Scholar 

  21. Roulier, E. M., Panzer, S. & Beckendorf, S. K. The Tec29 tyrosine kinase is required during Drosophila embryogenesis and interacts with Src64 in ring canal development. Mol. Cell 1, 819–829 (1998)

    Article  CAS  PubMed  Google Scholar 

  22. Brinster, R. L. Germline stem cell transplantation and transgenesis. Science 296, 2174–2176 (2002)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kramerova, I. A. & Kramerov, A. A. Mucinoprotein is a universal constituent of stable intercellular bridges in Drosophila melanogaster germ line and somatic cells. Dev. Dyn. 216, 349–360 (1999)

    Article  CAS  PubMed  Google Scholar 

  24. Tanimoto, H., Itoh, S., ten Dijke, P. & Tabata, T. Hedgehog creates a gradient of DPP activity in Drosophila wing imaginal discs. Mol. Cell 5, 59–71 (2000)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank R. Cox, B. Ohlstein and E. deCotto for comments on the manuscript.

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Authors and Affiliations

  1. Howard Hughes Medical Institute Research Laboratories, Department of Embryology, Carnegie Institution of Washington, 115 W. University Parkway, Baltimore, Maryland, 21210, USA

    Toshie Kai & Allan Spradling

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  1. Toshie Kai
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  2. Allan Spradling
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Correspondence to Allan Spradling.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Discussion

The number of germ cells initially present at the time of heat shock in L2 larval ovaries as shown in Figure 2 is discussed. (DOC 19 kb)

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Kai, T., Spradling, A. Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries. Nature 428, 564–569 (2004). https://doi.org/10.1038/nature02436

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