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Developmental BiologyVolume 424, Issue 1, 1 April 2017, Pages 10-17

Intestinal stem cell ablation reveals differential requirements for survival in response to chemical challenge(Article)(Open Access)

  • aDepartment of Molecular, Cell, and Developmental Biology, University of California-Los Angeles, Los Angeles, CA 90095, United States
  • bMolecular Biology Institute, University of California-Los Angeles, Los Angeles, CA 90095, United States
  • cEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California-Los Angeles, Los Angeles, CA 90095, United States

Abstract

The Drosophila intestine is maintained by multipotent intestinal stem cells (ISCs). Although increased intestinal stem cell (ISC) proliferation has been correlated with a decrease in longevity, there is some discrepancy regarding whether a decrease or block in proliferation also has negative consequences. Here we identify headcase (hdc) as a novel marker of ISCs and enteroblasts (EBs) and demonstrate that Hdc function is required to prevent ISC/EB loss through apoptosis. Hdc depletion was used as a strategy to ablate ISCs and EBs in order to test the ability of flies to survive without ISC function. While flies lacking ISCs showed no major decrease in survival under unchallenged conditions, flies depleted of ISCs and EBs exhibited decreased survival rates in response to damage to mature enterocytes (EC) that line the intestinal lumen. Our findings indicate that constant renewal of the intestinal epithelium is not absolutely necessary under normal laboratory conditions, but it is important in the context of widespread chemical-induced damage when significant repair is necessary. © 2017 Elsevier Inc.

Author keywords

DrosophilaHeadcaseIntestineNicheStem cell

Indexed keywords

EMTREE drug terms:cell markerheadcase proteinunclassified drugbiological markerbleomycinDrosophila proteinheadcase protein, Drosophila
EMTREE medical terms:animal tissueapoptosisArticlecell survivalcontrolled studyDrosophilaenteroblastintestinal stem cellintestine cellintestine epitheliummidgutnonhumantissue regenerationanimalcell survivalcytologyDrosophila melanogasterdrug effectsfemaleintestinemetabolismregenerationstem cell
MeSH:AnimalsApoptosisBiomarkersBleomycinCell SurvivalDrosophila melanogasterDrosophila ProteinsFemaleIntestinesRegenerationStem Cells

Chemicals and CAS Registry Numbers:

bleomycin, 11056-06-7, 9041-93-4;

Biomarkers; Bleomycin; Drosophila Proteins; headcase protein, Drosophila

Funding details

Funding sponsor Funding number Acronym
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles
National Institutes of Health
See opportunities		AG040288,AG028092
Amgen
See opportunities
Fuel Cell Technologies ProgramSFRH/BD/33253/2007FCT
University of California, Los Angeles
California Institute of Regenerative MedicineRN1-00544-1

  • 1

    The authors thank H. Jasper, D. Walker, S. Hou, B. Ohlstein, R. White, the Vienna Drosophila RNAi Center (VDRC), and Bloomington Stock Center for reagents and fly stocks, and are grateful to the Jones, Walker, and Sunkel laboratories for comments on the manuscript. We are also indebted to Cecilia D?Alterio for outstanding technical assistance. L.P.R. was a GABBA fellow funded by the Portuguese Foundation for Science and Technology (FCT; SFRH/BD/33253/2007), and M.E.T. was funded, in part, by the Amgen Scholars Program. This work was supported by the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles, the California Institute of Regenerative Medicine (RN1-00544-1), and the NIH (AG028092, AG040288 to D.L.J).

  • ISSN: 00121606
  • CODEN: DEBIA
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.ydbio.2017.01.004
  • PubMed ID: 28104389
  • Document Type: Article
  • Publisher: Academic Press Inc.

  Jones, D.L.; University of California, Department of Molecular, Cell, and Developmental Biology, 5139 Terasaki Life Sciences Building, Los Angeles, CA, United States;
© Copyright 2017 Elsevier B.V., All rights reserved.

Cited by 9 documents

Varga, G.I.B. , Csordás, G. , Cinege, G.
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The engineered gut: Use of stem cells and tissue engineering to study physiological mechanisms and disease processes: Intestinal renewal across the animal kingdom: Comparing stem cell activity in mouse and drosophila
(2019) American Journal of Physiology - Gastrointestinal and Liver Physiology
Xu, C. , Tang, H.-W. , Hung, R.-J.
The Septate Junction Protein Tsp2A Restricts Intestinal Stem Cell Activity via Endocytic Regulation of aPKC and Hippo Signaling
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