Isolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain

Abstract Background The naked mole-rat (NMR) is the longest-lived rodent with a maximum lifespan of more than 37 years and shows a negligible senescence phenotype, suggesting that tissue stem cells of NMRs are highly capable of maintaining homeostasis. However, the properties of NMR tissue stem cell...

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Autores principales: Yuki Yamamura, Yoshimi Kawamura, Yuki Oiwa, Kaori Oka, Nobuyuki Onishi, Hideyuki Saya, Kyoko Miura
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Publicado: BMC 2021
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spelling oai:doaj.org-article:50fb4623413c418db821bffc07ceb6912021-11-08T10:59:05ZIsolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain10.1186/s41232-021-00182-71880-8190https://doaj.org/article/50fb4623413c418db821bffc07ceb6912021-11-01T00:00:00Zhttps://doi.org/10.1186/s41232-021-00182-7https://doaj.org/toc/1880-8190Abstract Background The naked mole-rat (NMR) is the longest-lived rodent with a maximum lifespan of more than 37 years and shows a negligible senescence phenotype, suggesting that tissue stem cells of NMRs are highly capable of maintaining homeostasis. However, the properties of NMR tissue stem cells, including neural stem cells (NSCs), are largely unclear. Methods Neural stem/progenitor cells (NS/PCs) were isolated from the subventricular zone of the neonate NMR brain (NMR-NS/PCs) and cultured in neurosphere and adherent culture conditions. Expression of NSC markers and markers of neurons, astrocytes, and oligodendrocytes was analyzed by immunocytochemistry. In adherent culture conditions, the proliferation rate and cell cycle of NMR-NS/PCs were assessed and compared with those of NS/PCs from mice (mouse-NS/PCs). The DNA damage response to γ-irradiation was analyzed by immunocytochemistry and reverse transcription-quantitative PCR. Results NMR-NS/PCs expressed several NSC markers and differentiated into neurons, astrocytes, and oligodendrocytes. NMR-NS/PCs proliferated markedly slower than mouse-NS/PCs, and a higher percentage of NMR-NS/PCs than mouse-NS/PCs was in G0/G1 phase. Notably, upon γ-irradiation, NMR-NS/PCs exhibited a faster initiation of the DNA damage response and were less prone to dying than mouse-NS/PCs. Conclusions NMR-NS/PCs were successfully isolated and cultured. The slow proliferation of NMR-NS/PCs and their resistance to DNA damage may help to prevent stem cell exhaustion in the brain during the long lifespan of NMRs. Our findings provide novel insights into the mechanism underlying delayed aging of NMRs. Further analysis of NMR tissue stem cells may lead to the development of new strategies that can prevent aging in humans.Yuki YamamuraYoshimi KawamuraYuki OiwaKaori OkaNobuyuki OnishiHideyuki SayaKyoko MiuraBMCarticleNaked mole-ratNeural stem cellCell cycleCell proliferationDNA damage responsePathologyRB1-214ENInflammation and Regeneration, Vol 41, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Naked mole-rat
Neural stem cell
Cell cycle
Cell proliferation
DNA damage response
Pathology
RB1-214
spellingShingle Naked mole-rat
Neural stem cell
Cell cycle
Cell proliferation
DNA damage response
Pathology
RB1-214
Yuki Yamamura
Yoshimi Kawamura
Yuki Oiwa
Kaori Oka
Nobuyuki Onishi
Hideyuki Saya
Kyoko Miura
Isolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain
description Abstract Background The naked mole-rat (NMR) is the longest-lived rodent with a maximum lifespan of more than 37 years and shows a negligible senescence phenotype, suggesting that tissue stem cells of NMRs are highly capable of maintaining homeostasis. However, the properties of NMR tissue stem cells, including neural stem cells (NSCs), are largely unclear. Methods Neural stem/progenitor cells (NS/PCs) were isolated from the subventricular zone of the neonate NMR brain (NMR-NS/PCs) and cultured in neurosphere and adherent culture conditions. Expression of NSC markers and markers of neurons, astrocytes, and oligodendrocytes was analyzed by immunocytochemistry. In adherent culture conditions, the proliferation rate and cell cycle of NMR-NS/PCs were assessed and compared with those of NS/PCs from mice (mouse-NS/PCs). The DNA damage response to γ-irradiation was analyzed by immunocytochemistry and reverse transcription-quantitative PCR. Results NMR-NS/PCs expressed several NSC markers and differentiated into neurons, astrocytes, and oligodendrocytes. NMR-NS/PCs proliferated markedly slower than mouse-NS/PCs, and a higher percentage of NMR-NS/PCs than mouse-NS/PCs was in G0/G1 phase. Notably, upon γ-irradiation, NMR-NS/PCs exhibited a faster initiation of the DNA damage response and were less prone to dying than mouse-NS/PCs. Conclusions NMR-NS/PCs were successfully isolated and cultured. The slow proliferation of NMR-NS/PCs and their resistance to DNA damage may help to prevent stem cell exhaustion in the brain during the long lifespan of NMRs. Our findings provide novel insights into the mechanism underlying delayed aging of NMRs. Further analysis of NMR tissue stem cells may lead to the development of new strategies that can prevent aging in humans.
format article
author Yuki Yamamura
Yoshimi Kawamura
Yuki Oiwa
Kaori Oka
Nobuyuki Onishi
Hideyuki Saya
Kyoko Miura
author_facet Yuki Yamamura
Yoshimi Kawamura
Yuki Oiwa
Kaori Oka
Nobuyuki Onishi
Hideyuki Saya
Kyoko Miura
author_sort Yuki Yamamura
title Isolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain
title_short Isolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain
title_full Isolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain
title_fullStr Isolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain
title_full_unstemmed Isolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain
title_sort isolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain
publisher BMC
publishDate 2021
url https://doaj.org/article/50fb4623413c418db821bffc07ceb691
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