VIB Center for Brain & Disease Research, Leuven, Belgium; Laboratory of Computational Biology, Department of Human Genetics, University of Leuven, Leuven, Belgium
Ramya Balaji
Faculty of Biology, Hilde-Mangold-Haus, University of Freiburg, Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany
Dimitrije Stanković
Institute for Genetics Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Valerie M Christiaens
VIB Center for Brain & Disease Research, Leuven, Belgium; Laboratory of Computational Biology, Department of Human Genetics, University of Leuven, Leuven, Belgium
Carmen Bravo González-Blas
VIB Center for Brain & Disease Research, Leuven, Belgium; Laboratory of Computational Biology, Department of Human Genetics, University of Leuven, Leuven, Belgium
VIB Center for Brain & Disease Research, Leuven, Belgium; Laboratory of Computational Biology, Department of Human Genetics, University of Leuven, Leuven, Belgium
Gert J Hulselmans
VIB Center for Brain & Disease Research, Leuven, Belgium; Laboratory of Computational Biology, Department of Human Genetics, University of Leuven, Leuven, Belgium
Maxime De Waegeneer
VIB Center for Brain & Disease Research, Leuven, Belgium; Laboratory of Computational Biology, Department of Human Genetics, University of Leuven, Leuven, Belgium
Xiaojiang Quan
VIB Center for Brain & Disease Research, Leuven, Belgium; Laboratory of Computational Biology, Department of Human Genetics, University of Leuven, Leuven, Belgium
Duygu Koldere
VIB Center for Brain & Disease Research, Leuven, Belgium; Laboratory of Computational Biology, Department of Human Genetics, University of Leuven, Leuven, Belgium
Department of Biological Sciences, Sam Houston State University, Huntsville, United States
Georg Halder
VIB Center for Cancer Biology, Leuven, Belgium; Laboratory of Growth Control and Cancer Research, Department of Oncology, University of Leuven, Leuven, Belgium
Institute for Genetics Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Faculty of Biology, Hilde-Mangold-Haus, University of Freiburg, Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany
VIB Center for Brain & Disease Research, Leuven, Belgium; Laboratory of Computational Biology, Department of Human Genetics, University of Leuven, Leuven, Belgium
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 rasV12scrib-/- 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.
