Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-017-00935-4
Title: The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age
Authors: Hosokawa, K
MacArthur, B.D
Ikushima, Y.M
Toyama, H
Masuhiro, Y
Hanazawa, S
Suda, T 
Arai, F
Keywords: Pot1 protein
reactive oxygen metabolite
telomere binding protein
unclassified drug
DNA binding protein
POT1 protein, mouse
reactive oxygen metabolite
age
cells and cell components
chromosome
DNA
gene expression
protein
reactive oxygen species
animal cell
apoptosis
Article
cell activity
cell aging
cell differentiation
cell function
cell protection
cell survival
controlled study
DNA damage response
down regulation
ex vivo study
gene expression
hematopoietic stem cell
human
human cell
microarray analysis
mouse
nonhuman
oxidative phosphorylation
protein expression
protein function
rejuvenation
senescence
stem cell culture
stem cell expansion
stem cell self-renewal
animal
cell aging
cell culture
DNA damage
genetics
hematopoietic stem cell
metabolism
physiology
telomere
Animals
Cells, Cultured
Cellular Senescence
DNA Damage
DNA-Binding Proteins
Hematopoietic Stem Cells
Humans
Mice
Reactive Oxygen Species
Telomere
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Hosokawa, K, MacArthur, B.D, Ikushima, Y.M, Toyama, H, Masuhiro, Y, Hanazawa, S, Suda, T, Arai, F (2017). The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age. Nature Communications 8 (1) : 804. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-017-00935-4
Rights: Attribution 4.0 International
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. © 2017 The Author(s).
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/178570
ISSN: 2041-1723
DOI: 10.1038/s41467-017-00935-4
Rights: Attribution 4.0 International
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