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.

参与伤口修复的上皮细胞会对未来的损伤产生更有效的反应，这被认为是局部限制的。在这里，我们表明，局部组织损伤引起的细胞适应具有广泛的空间影响，其规模以前未曾认识到。我们证明，远离原始损伤的特定干细胞群起源于它们自己的生态位中的持久伤口记忆祖细胞。值得注意的是，这些远端记忆细胞并未参与第一次愈合，而是通过启动而在本质上被预激活。这种细胞状态维持在染色质和转录水平，可增强伤口修复，并通过表观遗传扰动部分重现。重要的是，伤口记忆会产生长期的有害后果，加剧肿瘤的发生。全面的，