Differential gene expression analysis identified determinants of cell fate plasticity during radiation-induced regeneration in Drosophila

PLoS Genet. 2022 Jan 6;18(1):e1009989. doi: 10.1371/journal.pgen.1009989. eCollection 2022 Jan.

Abstract

Ionizing radiation (IR) is used to treat half of all cancer patients because of its ability to kill cells. IR, however, can induce stem cell-like properties in non-stem cancer cells, potentiating tumor regrowth and reduced therapeutic success. We identified previously a subpopulation of cells in Drosophila larval wing discs that exhibit IR-induced stem cell-like properties. These cells reside in the future wing hinge, are resistant to IR-induced apoptosis, and are capable of translocating, changing fate, and participating in regenerating the pouch that suffers more IR-induced apoptosis. We used here a combination of lineage tracing, FACS-sorting of cells that change fate, genome-wide RNAseq, and functional testing of 42 genes, to identify two key changes that are required cell-autonomously for IR-induced hinge-to-pouch fate change: (1) repression of hinge determinants Wg (Drosophila Wnt1) and conserved zinc-finger transcription factor Zfh2 and (2) upregulation of three ribosome biogenesis factors. Additional data indicate a role for Myc, a transcriptional activator of ribosome biogenesis genes, in the process. These results provide a molecular understanding of IR-induced cell fate plasticity that may be leveraged to improve radiation therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Cell Plasticity
  • Cell Separation
  • Cell Survival / radiation effects
  • DNA-Binding Proteins / genetics
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Drosophila melanogaster / radiation effects
  • Exome Sequencing
  • Flow Cytometry
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Developmental / radiation effects
  • Larva / genetics
  • Larva / physiology
  • Larva / radiation effects
  • RNA-Seq
  • Regeneration / radiation effects*
  • Transcription Factors / genetics
  • Wings, Animal / physiology
  • Wings, Animal / radiation effects
  • Wnt1 Protein / genetics

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Myc protein, Drosophila
  • Transcription Factors
  • Wnt1 Protein
  • wg protein, Drosophila
  • Zfh2 protein, Drosophila