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Shared enhancer gene regulatory networks between wound and oncogenic programs

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE205401 | GEO | 2022/06/15

REPOSITORIES: GEO

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Shared enhancer gene regulatory networks between wound and oncogenic programs [RNA]

Project description:Wound response programs are often activated during neoplastic growth in tumors. In both systems, cells respond to acute stress and balance the activation of multiple programs including apoptosis, proliferation, and cell migration. Central to this response are the JNK/MAPK and JAK/STAT signaling pathways. Yet, to what extent these signaling cascades interact at the cis-regulatory level, and how they orchestrate different phenotypic responses is still unclear. Here, we aim to characterize the cellular states that emerge and cooperate in the wound response, using the Drosophila melanogaster wing disc as a model system. We used single-cell multi-omics profiling to derive enhancer Gene Regulatory Networks (eGRNs) from chromatin accessibility, transcription factor binding motif and gene expression signals. We identify the eGRNs being activated following a transient wound induction, and compare them with the scRNA profiles obtained from a persistent induction of the rasv12 scrib-/- oncogenic driver. We detect a small cell population in the wound that activates a senescence program that is shared with cancer cells. This population is characterized by the C/EBP-like transcription factors Irbp18, Xrp1, slow-border and vrille. Our single-cell multiome and eGRNs resource offers a new perspective on gene regulation in the normal and wounded wing disc.

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