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Centrosome misorientation reduces stem cell division during ageing

Author

Listed:
  • Jun Cheng

    (Center for Ultrafast Optical Science)

  • Nezaket Türkel

    (Life Sciences Institute, Center for Stem Cell Biology,
    Present address: Peter MacCallum Cancer Centre, Anatomy and Cell Biology Department, University of Melbourne, Melbourne, Victoria 3002, Australia.)

  • Nahid Hemati

    (Life Sciences Institute, Center for Stem Cell Biology,)

  • Margaret T. Fuller

    (Stanford University, School of Medicine, Stanford, California 94305, USA)

  • Alan J. Hunt

    (Center for Ultrafast Optical Science)

  • Yukiko M. Yamashita

    (Life Sciences Institute, Center for Stem Cell Biology,
    University of Michigan, Ann Arbor, Michigan 48109, USA)

Abstract

Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. A decline in stem cell function has been proposed to contribute to tissue ageing, although the underlying mechanism is poorly understood. Here we show that changes in the stem cell orientation with respect to the niche during ageing contribute to the decline in spermatogenesis in the male germ line of Drosophila. Throughout the cell cycle, centrosomes in germline stem cells (GSCs) are oriented within their niche and this ensures asymmetric division. We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. The cell cycle arrest is transient, and GSCs appear to re-enter the cell cycle on correction of centrosome orientation. On the basis of these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during ageing contributes to the decline in spermatogenesis. We also show that some of the misoriented GSCs probably originate from dedifferentiation of spermatogonia.

Suggested Citation

  • Jun Cheng & Nezaket Türkel & Nahid Hemati & Margaret T. Fuller & Alan J. Hunt & Yukiko M. Yamashita, 2008. "Centrosome misorientation reduces stem cell division during ageing," Nature, Nature, vol. 456(7222), pages 599-604, December.
    • Handle: RePEc:nat:nature:v:456:y:2008:i:7222:d:10.1038_nature07386
    DOI: 10.1038/nature07386
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    Cited by:

    1. Sharif M. Ridwan & Autumn Twillie & Samaneh Poursaeid & Emma Kristine Beard & Muhammed Burak Bener & Matthew Antel & Ann E. Cowan & Shinya Matsuda & Mayu Inaba, 2024. "Diffusible fraction of niche BMP ligand safeguards stem-cell differentiation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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