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The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age

Author

Listed:
  • Kentaro Hosokawa

    (Kyushu University
    Keio University)

  • Ben D. MacArthur

    (University of Southampton)

  • Yoshiko Matsumoto Ikushima

    (Keio University
    National Center for Global Health and Medicine)

  • Hirofumi Toyama

    (Keio University)

  • Yoshikazu Masuhiro

    (Nihon University)

  • Shigemasa Hanazawa

    (Nihon University)

  • Toshio Suda

    (Keio University
    National University of Singapore)

  • Fumio Arai

    (Kyushu University
    Keio University)

Abstract

Repeated cell divisions and aging impair stem cell function. However, the mechanisms by which this occurs are not fully understood. Here we show that protection of telomeres 1A (Pot1a), a component of the Shelterin complex that protects telomeres, improves haematopoietic stem cell (HSC) activity during aging. Pot1a is highly expressed in young HSCs, but declines with age. In mouse HSCs, Pot1a knockdown increases DNA damage response (DDR) and inhibits self-renewal. Conversely, Pot1a overexpression or treatment with POT1a protein prevents DDR, maintained self-renewal activity and rejuvenated aged HSCs upon ex vivo culture. Moreover, treatment of HSCs with exogenous Pot1a inhibits the production of reactive oxygen species, suggesting a non-telomeric role for Pot1a in HSC maintenance. Consistent with these results, treatment with exogenous human POT1 protein maintains human HSC activity in culture. Collectively, these results show that Pot1a/POT1 sustains HSC activity and can be used to expand HSC numbers ex vivo.

Suggested Citation

  • Kentaro Hosokawa & Ben D. MacArthur & Yoshiko Matsumoto Ikushima & Hirofumi Toyama & Yoshikazu Masuhiro & Shigemasa Hanazawa & Toshio Suda & Fumio Arai, 2017. "The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00935-4
    DOI: 10.1038/s41467-017-00935-4
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