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| Status |
Public on Feb 02, 2023 |
| Title |
Lifelong tissue memory relies on spatially organized dedicated progenitors located distally from the injury [bulkRNAseq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
It is believed epithelial cells that have participated in a wound repair elicit a more efficient but locally restricted response to future injuries. However here we show that the cell adaptation resulting from a localised tissue damage has a wide spatial impact at a scale not previously noticed. We demonstrate that away from injured site, after a first injury a specific epithelial stem cell population gives rise to long term wound-memory progenitors residing in their own niche of origin. Notably these progenitors have not taken part in the first wound healing but become pre-activated through priming. This adaptation differs from classical features of trained immunity previously shown to be adopted by other epithelial stem cells. Our newly identified wound-distal memory cells display an intrinsic pre-activated state, maintained at chromatin and transcriptional level, leading to an enhanced wound repair ability that can be partially recapitulated through epigenetic perturbation even in absence of an injury. Importantly, the harmful consequences of wound repair, such as exacerbated tumorigenesis, occur within these primed cells and follow their spatial distribution. Overall, we show that sub-organ scale adaptation of an injury relies on spatially organized and memory-dedicated progenitors, characterized by a chromatin actionable cell state, that establishes an epigenetic field cancerization and predisposes to tumour onset.
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| Overall design |
Lrig1 GL cells were isolated from tail epidermis at 8w pw1 from Distal memory or Ctrl region and FACS sorted to enrich for upper-HF cells (Sca1+). Cells were then plated and cultured for 1 week before transcriptome was assessed by bulk RNA-Seq
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| Contributor(s) |
Levron CL, Watanabe M, Proserpio V, Piacenti G, Lauria A, Kaltenbach S, Tamburrini A, Nohara T, Anselmi F, Duval C, Elettrico L, Donna D, Conti L, Baev D, Natsuga K, Hagai T, Oliviero S, Donati G |
| Citation missing |
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| |
| Submission date |
Dec 20, 2022 |
| Last update date |
Feb 02, 2023 |
| Contact name |
Andrea Lauria |
| E-mail(s) |
andrea.lauria@unito.it
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| Organization name |
University of Turin
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| Department |
Life Sciences and Systems Biology
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| Lab |
Functional Genomics, Epigenomics - S. Oliviero
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| Street address |
Via Accademia Albertina, 13
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| City |
Turin |
| ZIP/Postal code |
10123 |
| Country |
Italy |
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| Platforms (1) |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE197590 |
Wound memory of epidermal stem cells |
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| Relations |
| BioProject |
PRJNA914252 |
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