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Tie-mediated signal from apoptotic cells protects stem cells in Drosophila melanogaster

Yalan Xing1, Tin Tin Su2, Hannele Ruohola-Baker3

  • 1Department of Biochemistry, Institute for Stem Cell &Regenerative Medicine, University of Washington, Seattle Washington 98109, USA.

Nature Communications
|May 12, 2015
PubMed

Insights

Adult stem cells resist genotoxins via a survival signal from dying daughter cells. This mechanism involves microRNA bantam and protects stem cells, offering potential cancer stem cell eradication strategies.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Genetics

Background:

  • Normal and cancer stem cells exhibit resistance to genotoxins, yet the underlying mechanisms remain largely unknown.
  • Understanding stem cell resistance is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To investigate the mechanism of resistance to ionizing radiation (IR) in Drosophila melanogaster adult stem cells.
  • To identify signaling pathways involved in protecting stem cells from genotoxic stress.

Main Methods:

  • Utilized Drosophila melanogaster models to study germline and midgut stem cells.
  • Employed techniques including gene knockdown and analysis of microRNA and protein expression.
  • Investigated the role of the Tie/Tie-2 receptor tyrosine kinase pathway and its downstream targets.

Main Results:

  • Ionizing radiation activates the Tie/Tie-2 receptor tyrosine kinase pathway in stem cells.
  • This activation upregulates microRNA bantam, which represses FOXO-mediated transcription of the pro-apoptotic gene Hid.
  • Knockdown of the Tie ligand Pvf1 in differentiating daughter cells sensitizes stem cells to IR, indicating a survival signal from daughters.

Conclusions:

  • Dying daughter cells transmit a survival signal to protect stem cells from genotoxic damage.
  • This protective mechanism, involving microRNA bantam and the Tie pathway, is essential for tissue repopulation.
  • The conserved nature of this pathway suggests potential therapeutic strategies for eradicating cancer stem cells.

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