381B Poster - 04. Stem cells, regeneration and tissue injury
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Caitlin Clark ¹; Michelle Ledru ^1,3; Jeremy Brown ¹; Shay Segal ¹; Shilpi Verghese ^1,4; Sarah Ferrara ²; Andrew Goodspeed ²; Tin Tin Su ^1,2

Affiliations:
1) Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO; 2) University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, CO; 3) College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO ; 4) Department of Cell Biology, Emory University School of Medicine, Atlanta, GA

Keywords:
k. regeneration; b. death mutants/genes

Ionizing radiation (IR) is used to treat approximately half of all cancer patients due to its ability to induce cell death. However, IR can also induce cancer stem cell-like properties in non-stem cancer cells, potentially promoting tumor regeneration and diminishing therapeutic success. Our published studies have shown that we can model IR-inducible stem cell-like properties in Drosophila melanogaster larval imaginal wing discs. After irradiation, IR-resistant cells from the hinge-region of the disc translocate to the pouch-region of the disc and change fate to help regenerate the pouch (Verghese and Su, 2016, PMID: 27584613; Verghese and Su, 2018, PMID: 30462636). Genome-wide RNAseq analysis of dissociated wing disc cells identified IR-induced gene expression changes specific to the hinge such as down-regulation of hinge determinants and up-regulation of Myc targets and ribosome biogenesis genes. Functional testing shows that Myc and genes that function in ribosome biogenesis are required specifically in the hinge for IR-induced fate change (Ledru et al., in revision for PLoS Genetics). Current efforts are directed at using hinge-specific ribosome profiling to identify mRNAs whose increased translation promotes cell fate change after irradiation.