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

Yuki Yamamura, Yoshimi Kawamura, Yuki Oiwa, Kaori Oka, Nobuyuki Onishi, Hideyuki Saya, Kyoko Miura

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number31
JournalInflammation and Regeneration
Volume41
Issue number1
DOIs
Publication statusPublished - 2021 Dec

Keywords

  • Cell cycle
  • Cell proliferation
  • DNA damage response
  • Naked mole-rat
  • Neural stem cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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