MechanismsCells

Blind mole-rat mesenchymal stem cells resist carcinogen-induced damage through preserved p53 signaling

Unlike human and mouse cells, blind mole-rat stem cells maintained viability and differentiation after carcinogen exposure by preserving protective gene pathways.

A branching stem cell with an intact nucleus sits beside smaller spreading cells and shrunken cells with fragmented nuclei and scattered debris.

Stem Cells3 Oct 2026, 01:04 BST

Researchers evaluated how bone marrow-derived mesenchymal stem cells and fibroblasts from the Anatolian blind mole-rat (Nannospalax xanthodon) respond to the chemical carcinogen N-methyl-N-nitrosourea. The authors compared these cellular and transcriptomic responses against cells derived from mice, rats, and humans.

While carcinogen treatment triggered apoptosis and lowered viability in human and mouse stem cells, blind mole-rat stem cells maintained normal proliferation, viability, and multi-lineage differentiation potential. In blind mole-rat fibroblasts, exposure suppressed PI3K/Akt signaling and modulated mitochondrial oxidative phosphorylation. Meanwhile, blind mole-rat stem cells preserved cellular programming, sustained p53-mediated transcriptional regulation, and suppressed pro-tumoral SMAD signaling. Integrating these cross-species findings with human cancer datasets, the authors identified LAMTOR3 as a key p53-dependent node that helps protect blind mole-rat cells from malignant transformation.

Why it matters

Uncovering how naturally cancer-resistant species maintain stem cell integrity under genomic stress points to conserved molecular targets that could counter age-associated malignancies.

Caveats

The findings are based entirely on in vitro cell cultures challenged with a single chemical carcinogen, which may not reflect responses across an intact organism.