Adult stem cell activity in naked mole rats for long-term tissue maintenance

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Shamir Montazid - , University of Oxford (Author)
  • Sheila Bandyopadhyay - , Rutgers - The State University of New Jersey, New Brunswick (Author)
  • Daniel W. Hart - , University of Pretoria (Author)
  • Nan Gao - , Rutgers - The State University of New Jersey, New Brunswick (Author)
  • Brian Johnson - , University of California at San Diego (Author)
  • Sri G. Thrumurthy - , King's College Hospital NHS Foundation Trust (Author)
  • Dustin J. Penn - , University of Veterinary Medicine Vienna (Author)
  • Bettina Wernisch - , University of Veterinary Medicine Vienna (Author)
  • Mukesh Bansal - , Bristol-Myers Squibb (Author)
  • Philipp M. Altrock - , Max Planck Institute for Evolutionary Biology (Author)
  • Fabian Rost - , DRESDEN-concept Genome Center (CMCB Core Facility) (Author)
  • Patrycja Gazinska - , Polish Center for Technology Development (PORT) (Author)
  • Piotr Ziolkowski - , Wrocław Medical University (Author)
  • Bu’Hussain H. Hayee - , King's College Hospital NHS Foundation Trust (Author)
  • Yue Liu - , Rutgers - The State University of New Jersey, New Brunswick (Author)
  • Jiangmeng Han - , Rutgers - The State University of New Jersey, New Brunswick (Author)
  • Annamaria Tessitore - , University of Oxford (Author)
  • Jana Koth - , University of Oxford (Author)
  • Walter F. Bodmer - , University of Oxford (Author)
  • James E. East - , Oxford University Hospitals NHS Foundation Trust (Author)
  • Nigel C. Bennett - , University of Pretoria (Author)
  • Ian Tomlinson - , University of Oxford (Author)
  • Shazia Irshad - , University of Oxford (Author)

Abstract

The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity and tissue function with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5 +) in their native in vivo state, we find an expanded pool of Lgr5 + cells in NMRs, and these cells specifically at the crypt base (Lgr5 +CBC) exhibit slower division rates compared to those in short-lived mice but have a similar turnover as human LGR5 +CBC cells. Instead of entering quiescence (G0), NMR Lgr5 +CBC cells reduce their division rates by prolonging arrest in the G1 and/or G2 phases of the cell cycle. Moreover, we also observe a higher proportion of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust pro-apoptotic, anti-proliferative response within the stem/progenitor cell zone.

Details

Original languageEnglish
Article number8484
JournalNature communications
Volume14
Issue number1
Publication statusPublished - Dec 2023
Peer-reviewedYes

External IDs

PubMed 38123565
ORCID /0000-0001-6466-2589/work/149796652

Keywords

Keywords

  • Intestines, Animals, Humans, Intestinal Mucosa/metabolism, Receptors, G-Protein-Coupled/metabolism, Mole Rats, Mice, Longevity, Adult Stem Cells/metabolism