Intestinal Stem Cell Pool Regulation in Drosophila

Abstract

SummaryIntestinal epithelial renewal is mediated by intestinal stem cells (ISCs) that exist in a state of neutral drift, wherein individual ISC lineages are regularly lost and born but ISC numbers remain constant. To test whether an active mechanism maintains stem cell pools in the Drosophila midgut, we performed partial ISC depletion. In contrast to the mouse intestine, Drosophila ISCs failed to repopulate the gut after partial depletion. Even when the midgut was challenged to regenerate by infection, ISCs retained normal proportions of asymmetric division and ISC pools did not increase. We discovered, however, that the loss of differentiated midgut enterocytes (ECs) slows when ISC division is suppressed and accelerates when ISC division increases. This plasticity in rates of EC turnover appears to facilitate epithelial homeostasis even after stem cell pools are compromised. Our study identifies unique behaviors of Drosophila midgut cells that maintain epithelial homeostasis.

Lactobacillus Protects Against S. Typhimurium–Induced Intestinal Inflammation by Determining the Fate of Epithelial Proliferation and Differentiation

“…The proliferation of the intestinal epithelium due to the presence of intestinal stem cells (ISCs) constitutes the basis for the maintenance of the intestinal mucosal barrier against pathogen invasion and intestinal inflammation. [ The intestinal microbiota is continuously in contact with the epithelium and affects niches of ISCs to influence the proliferation and differentiation of the epithelium . Moreover, Wnt signaling directly controls cell fate, such as proliferation, differentiation, and apoptosis .…”

“…[[9,10] The intestinal microbiota is continuously in contact with the epithelium and affects niches of ISCs to influence the proliferation and differentiation of the epithelium. [11][12][13] Moreover, Wnt signaling directly controls cell fate, such as proliferation, differentiation, and apoptosis. [14] Dysregulation of the Wnt signaling pathway has been shown to be closely related to multiple tumorigenesis.…”

Recent Advances in Intestinal Stem Cells

“…In addition, a subset of reserve Lgr5+ cells are multipotent, marked by expression of Mex3A (an RNA binding protein), and can convert to fast-dividing ISCs to maintain homeostasis and regenerate the epithelium after chemotherapeutic injury [8]. In contrast to mice, drosophila midgut ISCs do not rapidly repopulate after induced depletion; rather, drosophila ISCs continue to divide asynchronously but enterocyte differentiation slows down to facilitate epithelial homeostasis [9]. It is hypothesized that this effect may be related to the short lifespan of the fly versus the comparatively long life of mice or humans.…”

“…It is hypothesized that this effect may be related to the short lifespan of the fly versus the comparatively long life of mice or humans. In the latter species, a responsive ISC pool of cells is actively maintained to undertake epithelial barrier injury recovery as well as removal of defective genetically damaged ISCs [9]. …”

Mono-Association withLactobacillus plantarumDisrupts Intestinal Homeostasis in adultDrosophila

“…For example, in flies and mammals, basal Intestinal Stem Cells (ISCs) divide and differentiate at a rate that maintains an intact epithelial barrier (20,22,(24)(25)(26). A relatively simple "escalator" program matches ISC division to loss of aged cells, while a more complex, adaptive program activates ISC division to compensate for environmental destruction of host cells (27). This adaptive regulation of growth maintains the integrity of the epithelial barrier, and is critical for long-term health of the host.…”