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

Shamir Montazid, Sheila Bandyopadhyay, Daniel W. Hart, Nan Gao, Brian Johnson, Sri G. Thrumurthy, Dustin J. Penn, Bettina Wernisch, Mukesh Bansal, Philipp M. Altrock, Fabian Rost, Patrycja Gazinska, Piotr Ziolkowski, Bu’Hussain Hayee, Yue Liu, Jiangmeng Han, Annamaria Tessitore, Jana Koth, Walter F. Bodmer, James E. East, Nigel C. Bennett, Ian Tomlinson () and Shazia Irshad ()
Additional contact information
Shamir Montazid: University of Oxford
Sheila Bandyopadhyay: Rutgers University
Daniel W. Hart: University of Pretoria
Nan Gao: Rutgers University
Brian Johnson: University of California San Diego, 9500 Gilman Dr
Sri G. Thrumurthy: Endoscopy, King’s College Hospital NHS Foundation Trust
Dustin J. Penn: University of Veterinary Medicine
Bettina Wernisch: University of Veterinary Medicine
Mukesh Bansal: Bristol Myers Squibb
Philipp M. Altrock: Max Planck Institute for Evolutionary Biology
Fabian Rost: DRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden
Patrycja Gazinska: Lukasiewicz Research Network, PORT Polish Center for Technology Development
Piotr Ziolkowski: Wroclaw Medical University
Bu’Hussain Hayee: Endoscopy, King’s College Hospital NHS Foundation Trust
Yue Liu: Rutgers University
Jiangmeng Han: Rutgers University
Annamaria Tessitore: Novo Nordisk Research Centre Oxford
Jana Koth: Weatherall Institute of Molecular Medicine, University of Oxford
Walter F. Bodmer: Weatherall Institute of Molecular Medicine, University of Oxford
James E. East: John Radcliffe Hospital, Headington
Nigel C. Bennett: University of Pretoria
Ian Tomlinson: University of Oxford
Shazia Irshad: University of Oxford

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-44138-6

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