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

  1. Jun Chen
  2. Na Xu
  3. Huagnwei Huang
  4. Tao Cai
  5. Rongwen Xi  Is a corresponding author
  1. Peking Union Medical College, China
  2. National Institute of Biological Sciences, China

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.

Article and author information

Author details

  1. Jun Chen

    Graduate Program, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Na Xu

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Huagnwei Huang

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Tao Cai

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Rongwen Xi

    National Institute of Biological Sciences, Beijing, China
    For correspondence
    xirongwen@nibs.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Allan C Spradling, Howard Hughes Medical Institute, Carnegie Institution for Science, United States

Version history

  1. Received: January 10, 2016
  2. Accepted: May 13, 2016
  3. Accepted Manuscript published: May 17, 2016 (version 1)
  4. Version of Record published: June 13, 2016 (version 2)
  5. Version of Record updated: February 7, 2017 (version 3)

Copyright

© 2016, Chen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jun Chen
  2. Na Xu
  3. Huagnwei Huang
  4. Tao Cai
  5. Rongwen Xi
(2016)
A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis
eLife 5:e14330.
https://doi.org/10.7554/eLife.14330

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https://doi.org/10.7554/eLife.14330

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