Shared enhancer gene regulatory networks between wound and oncogenic programs.

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.