Epigenetic memory of radiotherapy in dermal fibroblasts impairs wound repair capacity in cancer survivors.

ABSTRACT: Radiotherapy (RT), a common cancer treatment, unintentionally harms surrounding tissues, including the skin, and hinders wound healing years after treatment. This study aims to understand the mechanisms behind these late-onset adverse effects. We compare skin biopsies from previously irradiated (RT⁺) and non-irradiated (RT^-) sites in breast cancer survivors who underwent RT years ago. Here we show that the RT⁺ skin has compromised healing capacity and fibroblast functions. Using ATAC-seq, we discover altered chromatin landscapes in RT⁺ fibroblasts, with THBS1 identified as a crucial epigenetically primed wound repair-related gene. This is further confirmed by single-cell RNA-sequencing and spatial transcriptomic analysis of human wounds. Notably,

SUBMITTER: Bian X 

PROVIDER: S-EPMC11519383 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature