Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium
- Author
- Katja Horvay, Thierry Jardé, Franca Casagranda, Victoria M Perreau, Katharina Haigh (UGent) , Christian M Nefzger, Reyhan Akhtar, Thomas Gridley, Geert Berx (UGent) , Jody Haigh (UGent) , Nick Barker, Jose M Polo, Gary R Hime and Helen E Abud
- Organization
- Abstract
- Snail family members regulate epithelial-to-mesenchymal transition (EMT) during invasion of intestinal tumours, but their role in normal intestinal homeostasis is unknown. Studies in breast and skin epithelia indicate that Snail proteins promote an undifferentiated state. Here, we demonstrate that conditional knockout of Snai1 in the intestinal epithelium results in apoptotic loss of crypt base columnar stem cells and bias towards differentiation of secretory lineages. In vitro organoid cultures derived from Snai1 conditional knockout mice also undergo apoptosis when Snai1 is deleted. Conversely, ectopic expression of Snai1 in the intestinal epithelium in vivo results in the expansion of the crypt base columnar cell pool and a decrease in secretory enteroendocrine and Paneth cells. Following conditional deletion of Snai1, the intestinal epithelium fails to produce a proliferative response following radiation-induced damage indicating a fundamental requirement for Snai1 in epithelial regeneration. These results demonstrate that Snai1 is required for regulation of lineage choice, maintenance of CBC stem cells and regeneration of the intestinal epithelium following damage.
- Keywords
- apoptosis, intestinal stem cell, organoid, SerinC3, Snail, TRANSCRIPTION FACTOR SNAIL, MESENCHYMAL TRANSITION, IN-VITRO, CANCER INITIATION, PROGENITOR CELLS, GENE-EXPRESSION, RAPID LOSS, CRYPT, SLUG, DIFFERENTIATION
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-6887944
- MLA
- Horvay, Katja, et al. “Snai1 Regulates Cell Lineage Allocation and Stem Cell Maintenance in the Mouse Intestinal Epithelium.” EMBO JOURNAL, vol. 34, no. 10, 2015, pp. 1319–35, doi:10.15252/embj.201490881.
- APA
- Horvay, K., Jardé, T., Casagranda, F., Perreau, V. M., Haigh, K., Nefzger, C. M., … Abud, H. E. (2015). Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium. EMBO JOURNAL, 34(10), 1319–1335. https://doi.org/10.15252/embj.201490881
- Chicago author-date
- Horvay, Katja, Thierry Jardé, Franca Casagranda, Victoria M Perreau, Katharina Haigh, Christian M Nefzger, Reyhan Akhtar, et al. 2015. “Snai1 Regulates Cell Lineage Allocation and Stem Cell Maintenance in the Mouse Intestinal Epithelium.” EMBO JOURNAL 34 (10): 1319–35. https://doi.org/10.15252/embj.201490881.
- Chicago author-date (all authors)
- Horvay, Katja, Thierry Jardé, Franca Casagranda, Victoria M Perreau, Katharina Haigh, Christian M Nefzger, Reyhan Akhtar, Thomas Gridley, Geert Berx, Jody Haigh, Nick Barker, Jose M Polo, Gary R Hime, and Helen E Abud. 2015. “Snai1 Regulates Cell Lineage Allocation and Stem Cell Maintenance in the Mouse Intestinal Epithelium.” EMBO JOURNAL 34 (10): 1319–1335. doi:10.15252/embj.201490881.
- Vancouver
- 1.Horvay K, Jardé T, Casagranda F, Perreau VM, Haigh K, Nefzger CM, et al. Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium. EMBO JOURNAL. 2015;34(10):1319–35.
- IEEE
- [1]K. Horvay et al., “Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium,” EMBO JOURNAL, vol. 34, no. 10, pp. 1319–1335, 2015.
@article{6887944, abstract = {{Snail family members regulate epithelial-to-mesenchymal transition (EMT) during invasion of intestinal tumours, but their role in normal intestinal homeostasis is unknown. Studies in breast and skin epithelia indicate that Snail proteins promote an undifferentiated state. Here, we demonstrate that conditional knockout of Snai1 in the intestinal epithelium results in apoptotic loss of crypt base columnar stem cells and bias towards differentiation of secretory lineages. In vitro organoid cultures derived from Snai1 conditional knockout mice also undergo apoptosis when Snai1 is deleted. Conversely, ectopic expression of Snai1 in the intestinal epithelium in vivo results in the expansion of the crypt base columnar cell pool and a decrease in secretory enteroendocrine and Paneth cells. Following conditional deletion of Snai1, the intestinal epithelium fails to produce a proliferative response following radiation-induced damage indicating a fundamental requirement for Snai1 in epithelial regeneration. These results demonstrate that Snai1 is required for regulation of lineage choice, maintenance of CBC stem cells and regeneration of the intestinal epithelium following damage.}}, author = {{Horvay, Katja and Jardé, Thierry and Casagranda, Franca and Perreau, Victoria M and Haigh, Katharina and Nefzger, Christian M and Akhtar, Reyhan and Gridley, Thomas and Berx, Geert and Haigh, Jody and Barker, Nick and Polo, Jose M and Hime, Gary R and Abud, Helen E}}, issn = {{0261-4189}}, journal = {{EMBO JOURNAL}}, keywords = {{apoptosis,intestinal stem cell,organoid,SerinC3,Snail,TRANSCRIPTION FACTOR SNAIL,MESENCHYMAL TRANSITION,IN-VITRO,CANCER INITIATION,PROGENITOR CELLS,GENE-EXPRESSION,RAPID LOSS,CRYPT,SLUG,DIFFERENTIATION}}, language = {{eng}}, number = {{10}}, pages = {{1319--1335}}, title = {{Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium}}, url = {{http://doi.org/10.15252/embj.201490881}}, volume = {{34}}, year = {{2015}}, }
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