Intestinal stem cell ablation reveals differential requirements for survival in response to chemical challenge

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.

Pink1 and Parkin regulateDrosophilaintestinal stem cell proliferation during stress and aging

“…S3, D–F). We previously reported that flies lacking ISCs did not demonstrate decreased survival under control conditions; however, these flies had decreased rates of survival in response to bleomycin exposure ( Resende et al, 2017 ). Collectively, these data indicate that limited renewal of the midgut epithelium is sufficient to avoid premature death, but ISC/EB ablation can sensitize the animals to chemically induced damage.…”

Loss of foxo rescues stem cell aging in Drosophila germ line

“…Stem cells in Drosophila melanogaster are a versatile system with which to study age related changes in regenerative potential ( Lucchetta and Ohlstein, 2017 ; Fabian and Brill 2012 ; Resende et al, 2017 ; Resnik-Docampo et al, 2017 ). Defects in GSC function in aged flies have been identified and are in line with hypothesized defects in aging human stem cells: decreased proliferative capacity, accumulation of DNA damage, and eventual loss of stem cells ( Zhao et al, 2008 ; Kao et al, 2015 ).…”

Wnt Signalling in Intestinal Stem Cells: Lessons from Mice and Flies

“…Drosophila ISCs undergo cell division to renew themselves and generate uncommitted enteroblasts (EBs), which are progenitor cells that can further differentiate into either secretory enteroendocrine cells (EEs) or absorptive enterocytes (ECs) [ 44 ]. ISCs and EBs are characterized by the expression of the snail family transcription factor escargot ( esg ) [ 42 ] and headcase ( hdc ) [ 45 ]. Drosophila ISCs do not reside within discrete anatomical locations equivalent to the mammalian crypts and are instead scattered along the basal membrane of the intestinal epithelium.…”

“…Functional studies of ISCs in the adult Drosophila midgut are less complex. The discovery of esg [ 42 ] and, more recently, hdc [ 45 ] as markers of all stem/progenitor cells (ISCs/EBs), has allowed global targeting of this cell population and unambiguous assessment of their role in intestinal homeostasis and regeneration [ 45 , 79 ]. De-differentiation of committed lineages has not been reported in the adult Drosophila midgut, suggesting a lower degree of plasticity or reserve stem cell potential in the invertebrate tissue when compared to the mammalian intestine.…”