Tissue memory relies on stem cell priming in distal undamaged areas

Chiara Levra Levron, Mika Watanabe, Valentina Proserpio, Gabriele Piacenti, Andrea Lauria, Stefan Kaltenbach, Annalaura Tamburrini, Takuma Nohara, Francesca Anselmi, Carlotta Duval, Luca Elettrico, Daniela Donna, Laura Conti, Denis Baev, Ken Natsuga, Tzachi Hagai, Salvatore Oliviero, Giacomo Donati*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Epithelial cells that participated in wound repair elicit a more efficient response to future injuries, which is believed to be locally restricted. Here we show that cell adaptation resulting from a localized tissue damage has a wide spatial impact at a scale not previously appreciated. We demonstrate that a specific stem cell population, distant from the original injury, originates long-lasting wound memory progenitors residing in their own niche. Notably, these distal memory cells have not taken part in the first healing but become intrinsically pre-activated through priming. This cell state, maintained at the chromatin and transcriptional level, leads to an enhanced wound repair that is partially recapitulated through epigenetic perturbation. Importantly wound memory has long-term harmful consequences, exacerbating tumourigenesis. Overall, we show that sub-organ-scale adaptation to injury relies on spatially organized memory-dedicated progenitors, characterized by an actionable cell state that establishes an epigenetic field cancerization and predisposes to tumour onset.

Original languageEnglish
Pages (from-to)740-753
Number of pages14
JournalNature Cell Biology
Volume25
Issue number5
DOIs
StatePublished - May 2023

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