o:3002 Adult stem cell activity in naked mole rats for long-term tissue maintenance en 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. Mice; Humans; Animals; Longevity; Intestinal Mucosametabolism; Intestines; Adult Stem Cellsmetabolism; Receptors, G-Protein-Coupledmetabolism; Mole Rats 1552099 10.1038/s41467-023-44138-6 2024-05-17T11:34:09.435Z 44 yes 46 Shamir Montazid University of Oxford 0000-0002-4584-5619 Sheila Bandyopadhyay Rutgers University person Daniel W. Hart University of Pretoria person Nan Gao Rutgers University person Brian Johnson University of California person 0000-0002-9477-4677 Sri G. Thrumurthy King's College person Dustin J. Penn University of Veterinary Medicine Vienna person 0000-0002-5406-8065 Bettina Wernisch University of Veterinary Medicine Vienna person Mukesh Bansal Bristol Myers Squibb person Philipp M. Altrock Max Planck Institute for Evolutionary Biology person 0000-0001-7731-3345 Fabian Rost Technische Universität Dresden person 0000-0001-6466-2589 Patrycja Gazinska Polish Center for Technology Development person Piotr Ziolkowski Wroclaw Medical University person Bu'Hussain Hayee King's College person Yue Liu Rutgers University person Jiangmeng Han Rutgers University person Annamaria Tessitore Novo Nordisk Research Centre Oxford person Jana Koth University of Oxford person 0000-0002-6388-9308 Walter F. Bodmer University of Oxford person James E. East John Radcliffe Hospital person 0000-0001-8035-3700 Nigel C. Bennett University of Pretoria person Ian Tomlinson University of Oxford person 0000-0003-3037-1470 Shazia Irshad University of Oxford person 0000-0003-4536-373X application/pdf 2067301 https://phaidra.vetmeduni.ac.at/o:3002 no yes 16 70 1552253 Nature Communications 20 14 1 Nature Portfolio 2023