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

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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.

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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.
Na Xu

National Institute of Biological Sciences, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Huagnwei Huang

National Institute of Biological Sciences, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Tao Cai

National Institute of Biological Sciences, Beijing, China

Competing interests
The authors declare that no competing interests exist.
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.

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