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PMID:25959206

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Citation

Xing, Y, Su, TT and Ruohola-Baker, H (2015) Tie-mediated signal from apoptotic cells protects stem cells in Drosophila melanogaster. Nat Commun 6:7058

Abstract

Many types of normal and cancer stem cells are resistant to killing by genotoxins, but the mechanism for this resistance is poorly understood. Here we show that adult stem cells in Drosophila melanogaster germline and midgut are resistant to ionizing radiation (IR) or chemically induced apoptosis and dissect the mechanism for this protection. We find that upon IR the receptor tyrosine kinase Tie/Tie-2 is activated, leading to the upregulation of microRNA bantam that represses FOXO-mediated transcription of pro-apoptotic Smac/DIABLO orthologue, Hid in germline stem cells. Knockdown of the IR-induced putative Tie ligand, Pvf1, a functional homologue of human Angiopoietin, in differentiating daughter cells renders germline stem cells sensitive to IR, suggesting that the dying daughters send a survival signal to protect their stem cells for future repopulation of the tissue. If conserved in cancer stem cells, this mechanism may provide therapeutic options for the eradication of cancer.

Links

PubMed PMC4451836 Online version:10.1038/ncomms8058

Keywords

Animals; Apoptosis/physiology; Drosophila melanogaster/metabolism; Gene Deletion; Gene Expression Regulation, Enzymologic/physiology; Radiation, Ionizing; Receptor, TIE-2; Receptors, TIE/genetics; Receptors, TIE/metabolism; Signal Transduction; Stem Cells/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:Q9VKW2

involved_in

GO:0042078: germ-line stem cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VKW2

involved_in

GO:0036335: intestinal stem cell homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VKW2

involved_in

GO:0035019: somatic stem cell population maintenance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9NGN6

involved_in

GO:0035019: somatic stem cell population maintenance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9NGN6

involved_in

GO:0036335: intestinal stem cell homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9NGN6

involved_in

GO:0042078: germ-line stem cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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