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.
