Tissue-resident stem cell activity: a view from the adult Drosophila gastrointestinal tract

Abstract

The gastrointestinal tract serves as a fast-renewing model for unraveling the multifaceted molecular mechanisms underlying remarkably rapid cell renewal, which is exclusively fueled by a small number of long-lived stem cells and their progeny. Stem cell activity is the best-characterized aspect of mucosal homeostasis in mitotically active tissues, and the dysregulation of regenerative capacity is a hallmark of epithelial immune defects. This dysregulation is frequently associated with pathologies ranging from chronic enteritis to malignancies in humans. Application of the adult Drosophila gastrointestinal tract model in current and future studies to analyze the immuno-physiological aspects of epithelial defense strategies, including stem cell behavior and re-epithelialization, will be necessary to improve our general understanding of stem cell participation in epithelial turnover. In this review, which describes exciting observations obtained from the adult Drosophila gastrointestinal tract, we summarize a remarkable series of recent findings in the literature to decipher the molecular mechanisms through which stem cells respond to nonsterile environments.

Coordinated repression of pro-differentiation genes via P-bodies and transcription maintains Drosophila intestinal stem cell identity

“…The transcriptional repression of differentiation genes by the transcription factor esg is a key regulatory step of intestinal stem cell maintenance. 50,51,[59][60][61][62] The loss of esg gene expression or inability to localize the Esg protein to target genes promotes progenitor loss via premature ISC-to-EC differentiation. 50,51 Similar to Patr-1 RNAi, knocking down esg itself as well as either vtd, Nipped-B, or polo, all of which are necessary for recruiting Esg to target promoters, markedly upregulated the expression of Pdm1 in intestinal progenitors.…”

Coordinate transcriptional and post-transcriptional repression of pro-differentiation genes maintains intestinal stem cell identity

“…Based on our data, the weak transcription of pro-differentiation genes likely maintains progenitor cells in a primed state where differentiation program can be initiated rapidly and independent of transcription of differentiation genes. The transcriptional repression of differentiation genes by the transcription factor esg is a key regulatory step of intestinal stem cell maintenance (Antonello et al, 2015; Khaminets et al, 2020; Korzelius et al, 2014; Li et al, 2017; Liu and Jin, 2017; Loza-Coll et al, 2014). The loss of esg gene expression or inability to localize the Esg protein to target genes promote progenitor cell loss via premature ISC-to-EC differentiation (Khaminets et al, 2020; Korzelius et al, 2014).…”

“…esg is a key regulatory step of intestinal stem cell maintenance (Antonello et al, 2015;Khaminets et al, 2020;Korzelius et al, 2014;Li et al, 2017;Liu and Jin, 2017;Loza-Coll et al, 2014). For instance, the loss of Esg protein activity promotes ISC-to-EE differentiation through modulation of Notch activity via upregulating Amun, an inhibitor of Notch (Loza-Coll et al, 2014).…”

Sox100B Regulates Progenitor-Specific Gene Expression and Cell Differentiation in the Adult Drosophila Intestine

“…The last decade has witnessed significant advances in understanding the mechanisms by which ISC activities are regulated in response to infection, tissue injury, and during aging, with a strong focus on ISC proliferation (Guo et al, 2016;Jiang et al, 2016;Li and Jasper, 2016;Liu and Jin, 2017). In contrast, a well-defined progressive differentiation process is still inadequately understood.…”