RRC ID 36284
著者 Xing Y, Su TT, Ruohola-Baker H.
タイトル Tie-mediated signal from apoptotic cells protects stem cells in Drosophila melanogaster.
ジャーナル Nat Commun
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.
巻・号 6
ページ 7058
公開日 2015-5-11
DOI 10.1038/ncomms8058
PII ncomms8058
PMID 25959206
PMC PMC4451836
MeSH 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*
IF 12.121
引用数 23
WOS 分野 CELL BIOLOGY
リソース情報
ショウジョウバエ DGRC#114544