A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis

Elife. 2016 May 17;5:e14330. doi: 10.7554/eLife.14330.

Abstract

Homeostatic renewal of many adult tissues requires balanced self-renewal and differentiation of local stem cells, but the underlying mechanisms are poorly understood. Here we identified a novel feedback mechanism in controlling intestinal regeneration and tumorigenesis in Drosophila. Sox21a, a group B Sox protein, is preferentially expressed in the committed progenitor named enteroblast (EB) to promote enterocyte differentiation. In Sox21a mutants, EBs do not divide, but cannot differentiate properly and have increased expression of mitogens, which then act as paracrine signals to promote intestinal stem cell (ISC) proliferation. This leads to a feedback amplification loop for rapid production of differentiation-defective EBs and tumorigenesis. Notably, in normal intestine following damage, Sox21a is temporally downregulated in EBs to allow the activation of the ISC-EB amplification loop for epithelial repair. We propose that executing a feedback amplification loop between stem cells and their progeny could be a common mechanism underlying tissue regeneration and tumorigenesis.

Keywords: D. melanogaster; Sox21a; Spitz; cell biology; damage-induced regeneration; developmental biology; enteroblast; intestinal stem cell; stem cells; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis*
  • Cell Differentiation*
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Enterocytes / physiology*
  • Feedback*
  • Regeneration*
  • SOXB2 Transcription Factors / metabolism*
  • Stem Cells / physiology*

Substances

  • Drosophila Proteins
  • SOXB2 Transcription Factors
  • Sox21a protein, Drosophila melanogaster

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.