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

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 inte...

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Main Authors: Montazid, S, Bandyopadhyay, S, Hart, DW, Tessitore, A, Koth, J, Bodmer, W, East, J, Tomlinson, I, Irshad, S
Format: Journal article
Language:English
Published: Springer Nature 2023
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author Montazid, S
Bandyopadhyay, S
Hart, DW
Tessitore, A
Koth, J
Bodmer, W
East, J
Tomlinson, I
Irshad, S
author_facet Montazid, S
Bandyopadhyay, S
Hart, DW
Tessitore, A
Koth, J
Bodmer, W
East, J
Tomlinson, I
Irshad, S
author_sort Montazid, S
collection OXFORD
description 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.
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spelling oxford-uuid:780a08a3-e718-419c-9b52-4bee8d81c6022024-03-06T11:46:18ZAdult stem cell activity in naked mole rats for long-term tissue maintenanceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:780a08a3-e718-419c-9b52-4bee8d81c602EnglishSymplectic ElementsSpringer Nature2023Montazid, SBandyopadhyay, SHart, DWTessitore, AKoth, JBodmer, WEast, JTomlinson, IIrshad, SThe 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.
spellingShingle Montazid, S
Bandyopadhyay, S
Hart, DW
Tessitore, A
Koth, J
Bodmer, W
East, J
Tomlinson, I
Irshad, S
Adult stem cell activity in naked mole rats for long-term tissue maintenance
title Adult stem cell activity in naked mole rats for long-term tissue maintenance
title_full Adult stem cell activity in naked mole rats for long-term tissue maintenance
title_fullStr Adult stem cell activity in naked mole rats for long-term tissue maintenance
title_full_unstemmed Adult stem cell activity in naked mole rats for long-term tissue maintenance
title_short Adult stem cell activity in naked mole rats for long-term tissue maintenance
title_sort adult stem cell activity in naked mole rats for long term tissue maintenance
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