Wound response programs are often activated during neoplastic growth in tumors. In both wound repair and tumor growth, cells respond to acute stress and balance the activation of multiple programs, including apoptosis, proliferation, and cell migration. Central to those responses are the activation of 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 regulatory and phenotypic responses is still unclear. Here, we aim to characterize the regulatory states that emerge and cooperate in the wound response, using the Drosophila melanogaster wing disc as a model system, and compare these with cancer cell states induced by ras^V12scrib^-/- in the eye disc. We used single-cell multiome profiling to derive enhancer gene regulatory networks (eGRNs) by integrating chromatin accessibility and gene expression signals. We identify a ‘proliferative’ eGRN, active in the majority of wounded cells and controlled by AP-1 and STAT. In a smaller, but distinct population of wound cells, a ‘senescent’ eGRN is activated and driven by C/EBP-like transcription factors (Irbp18, Xrp1, Slow border, and Vrille) and Scalloped. These two eGRN signatures are found to be active in tumor cells at both gene expression and chromatin accessibility levels. Our single-cell multiome and eGRNs resource offers an in-depth characterization of the senescence markers, together with a new perspective on the shared gene regulatory programs acting during wound response and oncogenesis.

Inhibition is crucial for brain function, regulating network activity by balancing excitation and implementing gain control. Recent evidence suggests that beyond simply inhibiting excitatory activity, inhibitory neurons can also shape circuit function through disinhibition. While disinhibitory circuit motifs have been implicated in cognitive processes including learning, attentional selection, and input gating, the role of disinhibition is largely unexplored in the study of decision-making. Here, we show that disinhibition provides a simple circuit motif for fast, dynamic control of network state and function. This dynamic control allows a disinhibition-based decision model to reproduce both value normalization and winner-take-all dynamics, the two central features of neurobiological decision-making captured in separate existing models with distinct circuit motifs. In addition, the disinhibition model exhibits flexible attractor dynamics consistent with different forms of persistent activity seen in working memory. Fitting the model to empirical data shows it captures well both the neurophysiological dynamics of value coding and psychometric choice behavior. Furthermore, the biological basis of disinhibition provides a simple mechanism for flexible top-down control of the network states, enabling the circuit to capture diverse task-dependent neural dynamics. These results suggest a biologically plausible unifying mechanism for decision-making and emphasize the importance of local disinhibition in neural processing.