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

Kentaro Hosokawa, Ben D. MacArthur, Yoshiko Matsumoto Ikushima, Hirofumi Toyama, Yoshikazu Masuhiro, Shigemasa Hanazawa, Toshio Suda () and Fumio Arai ()
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Kentaro Hosokawa: Kyushu University
Ben D. MacArthur: University of Southampton
Yoshiko Matsumoto Ikushima: Keio University
Hirofumi Toyama: Keio University
Yoshikazu Masuhiro: Nihon University
Shigemasa Hanazawa: Nihon University
Toshio Suda: Keio University
Fumio Arai: Kyushu University

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00935-4

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