Regional signals in the planarian body guide stem cell fate in the presence of genomic instability

Development. 2016 May 15;143(10):1697-709. doi: 10.1242/dev.131318. Epub 2016 Mar 24.

Abstract

Cellular fate decisions are influenced by their topographical location in the adult body. For instance, tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. However, the molecular underpinnings of these regional differences are unknown. We identified a regional switch in the adult planarian body upon systemic disruption of homologous recombination with RNA-interference of Rad51 Rad51 knockdown increases DNA double-strand breaks (DSBs) throughout the body, but stem cells react differently depending on their location along the anteroposterior axis. In the presence of extensive DSBs, cells in the anterior part of the body resist death, whereas cells in the posterior region undergo apoptosis. Furthermore, we found that proliferation of cells with DNA damage is induced in the presence of brain tissue and that the retinoblastoma pathway enables overproliferation of cells with DSBs while attending to the demands of tissue growth and repair. Our results implicate both autonomous and non-autonomous mechanisms as key mediators of regional cell behavior and cellular transformation in the adult body.

Keywords: DNA damage; Neoblast; Planarian; Rad51; Stem cells.

Publication types

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

MeSH terms

  • Animals
  • Body Patterning / radiation effects
  • Cell Death / radiation effects
  • Cell Differentiation / radiation effects
  • Cell Division / radiation effects
  • Cell Lineage* / radiation effects
  • Cell Proliferation / radiation effects
  • DNA / metabolism
  • DNA Breaks, Double-Stranded / radiation effects
  • DNA Damage
  • DNA End-Joining Repair / radiation effects
  • Down-Regulation / radiation effects
  • Gamma Rays
  • Genomic Instability* / radiation effects
  • Homologous Recombination / radiation effects
  • Organ Specificity / radiation effects
  • Planarians / cytology*
  • Planarians / genetics*
  • Planarians / radiation effects
  • RNA Interference / radiation effects
  • Rad51 Recombinase / metabolism
  • Radiation, Ionizing
  • Retinoblastoma Protein / metabolism
  • Signal Transduction / radiation effects
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Stem Cells / radiation effects
  • Wound Healing / radiation effects

Substances

  • Retinoblastoma Protein
  • DNA
  • Rad51 Recombinase