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, Fumio Arai

研究成果: ジャーナルへの寄稿記事

8 引用 (Scopus)

抄録

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.

元の言語英語
記事番号804
ジャーナルNature communications
8
発行部数1
DOI
出版物ステータス出版済み - 12 1 2017

Fingerprint

Telomere-Binding Proteins
telomeres
stem cells
Telomere
Hematopoietic Stem Cells
Stem cells
proteins
Aging of materials
DNA Damage
deoxyribonucleic acid
DNA
damage
cell division
Cell culture
Cell Aging
Reactive Oxygen Species
Cells
Cell Division
maintenance
mice

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

これを引用

The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age. / Hosokawa, Kentaro; MacArthur, Ben D.; Ikushima, Yoshiko Matsumoto; Toyama, Hirofumi; Masuhiro, Yoshikazu; Hanazawa, Shigemasa; Suda, Toshio; Arai, Fumio.

:: Nature communications, 巻 8, 番号 1, 804, 01.12.2017.

研究成果: ジャーナルへの寄稿記事

Hosokawa, Kentaro ; MacArthur, Ben D. ; Ikushima, Yoshiko Matsumoto ; Toyama, Hirofumi ; Masuhiro, Yoshikazu ; Hanazawa, Shigemasa ; Suda, Toshio ; Arai, Fumio. / The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age. :: Nature communications. 2017 ; 巻 8, 番号 1.
@article{2e0307084e4a405c94f1b29404431bff,
title = "The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age",
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.",
author = "Kentaro Hosokawa and MacArthur, {Ben D.} and Ikushima, {Yoshiko Matsumoto} and Hirofumi Toyama and Yoshikazu Masuhiro and Shigemasa Hanazawa and Toshio Suda and Fumio Arai",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41467-017-00935-4",
language = "English",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age

AU - Hosokawa, Kentaro

AU - MacArthur, Ben D.

AU - Ikushima, Yoshiko Matsumoto

AU - Toyama, Hirofumi

AU - Masuhiro, Yoshikazu

AU - Hanazawa, Shigemasa

AU - Suda, Toshio

AU - Arai, Fumio

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85030786524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030786524&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-00935-4

DO - 10.1038/s41467-017-00935-4

M3 - Article

C2 - 28986560

AN - SCOPUS:85030786524

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 804

ER -