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Updated: Jul 31, 2025

Murine Excisional Wound Healing Model and Histological Morphometric Wound Analysis
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Shared enhancer gene regulatory networks between wound and oncogenic programs.

Swann Floc'hlay1,2, Ramya Balaji3,4, Dimitrije Stanković5

  • 1VIB Center for Brain & Disease Research, Leuven, Belgium.

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Summary

Cellular stress activates wound repair and tumor growth pathways. This study identifies shared gene regulatory networks, including

Keywords:
D. melanogastercancerchromatin accessibilitycomputational biologyenhancergene regulatory networksingle-cell multiomicssystems biologywound response

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Area of Science:

  • Cellular biology
  • Developmental biology
  • Cancer research

Background:

  • Wound repair and tumor growth share activated cellular programs like apoptosis, proliferation, and migration.
  • JNK/MAPK and JAK/STAT signaling pathways are central to these responses.
  • The precise interaction of these pathways at the cis-regulatory level and their orchestration of cellular phenotypes remain unclear.

Purpose of the Study:

  • To characterize cooperating regulatory states during wound response.
  • To compare these states with cancer cell states induced by ras^scrib.
  • To elucidate shared gene regulatory programs in wound healing and oncogenesis.

Main Methods:

  • Utilized Drosophila melanogaster wing and eye discs as model systems.
  • Employed single-cell multiome profiling to integrate chromatin accessibility and gene expression data.
  • Derived enhancer gene regulatory networks (eGRNs) to map regulatory states.

Main Results:

  • Identified a 'proliferative' eGRN, regulated by AP-1 and STAT, in most wounded cells.
  • Discovered a distinct 'senescent' eGRN, driven by C/EBP-like factors and Scalloped, in a subset of wound cells.
  • Confirmed the presence of both eGRN signatures in tumor cells at gene expression and chromatin accessibility levels.

Conclusions:

  • The study reveals shared gene regulatory programs between wound response and oncogenesis.
  • Characterized distinct proliferative and senescent eGRNs active in wound healing.
  • Provides a novel perspective on senescence markers and their role in shared regulatory programs during cancer development.