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A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905741/ https://www.ncbi.nlm.nih.gov/pubmed/27187149 http://dx.doi.org/10.7554/eLife.14330 |
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author | Chen, Jun Xu, Na Huang, Huanwei Cai, Tao Xi, Rongwen |
author_facet | Chen, Jun Xu, Na Huang, Huanwei Cai, Tao Xi, Rongwen |
author_sort | Chen, Jun |
collection | PubMed |
description | 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. DOI: http://dx.doi.org/10.7554/eLife.14330.001 |
format | Online Article Text |
id | pubmed-4905741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-49057412016-06-15 A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis Chen, Jun Xu, Na Huang, Huanwei Cai, Tao Xi, Rongwen eLife Cell Biology 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. DOI: http://dx.doi.org/10.7554/eLife.14330.001 eLife Sciences Publications, Ltd 2016-05-17 /pmc/articles/PMC4905741/ /pubmed/27187149 http://dx.doi.org/10.7554/eLife.14330 Text en © 2016, Chen et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Chen, Jun Xu, Na Huang, Huanwei Cai, Tao Xi, Rongwen A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis |
title | A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis |
title_full | A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis |
title_fullStr | A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis |
title_full_unstemmed | A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis |
title_short | A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis |
title_sort | feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905741/ https://www.ncbi.nlm.nih.gov/pubmed/27187149 http://dx.doi.org/10.7554/eLife.14330 |
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