GEO series
Epigenetic memory of radiotherapy in dermal fibroblasts impairs wound repair capacity in cancer survivors (ATAC-Seq)
GSE254753
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
45 samples
Submitted 2024/08/02
Platform GPL34284Platform GPL34290Platform GPL24676
Summary
Long-term toxicities caused by cancer treatments have recently gained increasing recognition due to a steadily growing population of cancer survivors. Radiotherapy (RT) is a common treatment known to unintentionally harm surrounding normal tissues including the skin, hindering wound healing even years after treatment. Our study aimed to elucidate the underlying mechanisms of these late-onset adverse effects caused by RT. By comparing paired skin biopsies from previously irradiated (RT+) and non-irradiated (RT-) sites in breast cancer survivors who underwent RT years ago, we discovered compromised wound healing capacity and impaired fibroblast functions in the RT+ skin. By employing ATAC-seq, we identified altered chromatin landscapes in RT+ fibroblasts, pinpointing THBS1 as a crucial epigenetically primed wound repair-related gene. Further confirmation of THBS1's significance during wound repair came from single-cell RNA-sequencing and spatial transcriptomic analysis of human wounds. Remarkably, heightened and sustained THBS1 expression was observed in RT+ fibroblasts in both mouse and human radiation wound models, leading to impaired fibroblast motility and contractility. Encouragingly, our study found that treatment with anti-THBS1 antibodies promoted ex vivo wound closure in RT+ skin from breast cancer survivors. These findings indicate that dermal fibroblasts retain a long-term radiation memory recorded in the form of epigenetic changes. Targeting this maladaptive epigenetic memory shows promise for mitigating the late-onset adverse effects caused by RT, offering potential solutions to improve the quality of life for cancer survivors.
Published in
Bian X, Piipponen M, Liu Z et al.
· Nature communications 2024
· PMID 39468077
· doi:10.1038/s41467-024-53295-1
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE254753_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 45 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1071623 and SRA study SRP487188. Searching any of these in the dataset finder brings you back here.
Study design
29 conditions, each sampled once — no replicated groups
Bulk ATAC-seq Ctr_D14 ×3
Bulk ATAC-seq IR_D14 ×3
Bulk ATAC-seq IR dermal fibroblasts D1 ×3
Bulk ATAC-seq Ctr_D1 ×2
Bulk ATAC-seq IR_D1 ×2
Bulk ATAC-seq Ctr_D7 ×2
Bulk ATAC-seq IR_D7 ×2
Bulk ATAC-seq Ctr dermal fibroblasts ×2
Read from the first 40 of 45 sample titles: 29 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8057187 Bulk ATAC-seq RS2_RT-
- GSM8057188 Bulk ATAC-seq RS2_RT+
- GSM8057189 Bulk ATAC-seq RS3_RT-
- GSM8057190 Bulk ATAC-seq RS3_RT+
- GSM8057191 Bulk ATAC-seq RS4_RT-
- GSM8057192 Bulk ATAC-seq RS4_RT+
- GSM8057193 Bulk ATAC-seq RS5_RT-
- GSM8057194 Bulk ATAC-seq RS5_RT+
- GSM8057195 Bulk ATAC-seq RS6_RT-
- GSM8057196 Bulk ATAC-seq RS6_RT+
- GSM8057197 Bulk ATAC-seq RS17_RT-
- GSM8057198 Bulk ATAC-seq RS17_RT+
- GSM8057199 Bulk ATAC-seq RS26_RT-
- GSM8057200 Bulk ATAC-seq RS26_RT+
- GSM8057201 Bulk ATAC-seq Ctr_D1_1
- GSM8057202 Bulk ATAC-seq Ctr_D1_2
- GSM8057203 Bulk ATAC-seq IR_D1_1
- GSM8057204 Bulk ATAC-seq IR_D1_2
- GSM8057205 Bulk ATAC-seq Ctr_D7_1
- GSM8057206 Bulk ATAC-seq Ctr_D7_2
- GSM8057207 Bulk ATAC-seq IR_D7_1
- GSM8057208 Bulk ATAC-seq IR_D7_2
- GSM8349818 Bulk ATAC-seq RS47 RT- S-
- GSM8349819 Bulk ATAC-seq RS47 RT- S+
- GSM8349820 Bulk ATAC-seq RS48 RT- S-
- GSM8349821 Bulk ATAC-seq RS48 RT- S+
- GSM8349822 Bulk ATAC-seq RS49 RT- S-
- GSM8349823 Bulk ATAC-seq RS49 RT- S+
- GSM8349824 Bulk ATAC-seq Ctr_D14_1
- GSM8349825 Bulk ATAC-seq Ctr_D14_2
- GSM8349826 Bulk ATAC-seq Ctr_D14_3
- GSM8349827 Bulk ATAC-seq IR_D14_1
- GSM8349828 Bulk ATAC-seq IR_D14_2
- GSM8349829 Bulk ATAC-seq IR_D14_3
- GSM8349830 Bulk ATAC-seq Ctr dermal fibroblasts 1
- GSM8349831 Bulk ATAC-seq Ctr dermal fibroblasts 2
- GSM8349832 Bulk ATAC-seq IR dermal fibroblasts D1-1
- GSM8349833 Bulk ATAC-seq IR dermal fibroblasts D1-2
- GSM8349834 Bulk ATAC-seq IR dermal fibroblasts D1-3
- GSM8349835 Bulk ATAC-seq Ctr dermal cell 1
+ 5 more — browse all 45 samples with per-sample file links →
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