The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation
The human intestine is covered by epithelium, which is continuously replaced by new cells provided by stem cells located at the bottom of the glands. The maintenance of intestinal stem cells is supported by a niche which is composed of several signaling proteins including the Hippo pathway effectors...
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MDPI AG
2020-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/8/1895 |
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| author | Sepideh Fallah Jean-François Beaulieu |
| author_facet | Sepideh Fallah Jean-François Beaulieu |
| author_sort | Sepideh Fallah |
| collection | DOAJ |
| description | The human intestine is covered by epithelium, which is continuously replaced by new cells provided by stem cells located at the bottom of the glands. The maintenance of intestinal stem cells is supported by a niche which is composed of several signaling proteins including the Hippo pathway effectors YAP1/TAZ. The role of YAP1/TAZ in cell proliferation and regeneration is well documented but their involvement on the differentiation of intestinal epithelial cells is unclear. In the present study, the role of YAP1/TAZ on the differentiation of intestinal epithelial cells was investigated using the HT29 cell line, the only multipotent intestinal cell line available, with a combination of knockdown approaches. The expression of intestinal differentiation cell markers was tested by qPCR, Western blot, indirect immunofluorescence and electron microscopy analyses. The results show that TAZ is not expressed while the abolition of YAP1 expression led to a sharp increase in goblet and absorptive cell differentiation and reduction of some stem cell markers. Further studies using double knockdown experiments revealed that most of these effects resulting from YAP1 abolition are mediated by CDX2, a key intestinal cell transcription factor. In conclusion, our results indicate that YAP1/TAZ negatively regulate the differentiation of intestinal epithelial cells through the inhibition of CDX2 expression. |
| first_indexed | 2024-03-10T17:30:27Z |
| format | Article |
| id | doaj.art-2ee3c4f2b4e94ade8fbd0c25be722745 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T17:30:27Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2ee3c4f2b4e94ade8fbd0c25be7227452023-11-20T10:01:38ZengMDPI AGCells2073-44092020-08-0198189510.3390/cells9081895The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell DifferentiationSepideh Fallah0Jean-François Beaulieu1Laboratory of Intestinal Physiopathology, Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaLaboratory of Intestinal Physiopathology, Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaThe human intestine is covered by epithelium, which is continuously replaced by new cells provided by stem cells located at the bottom of the glands. The maintenance of intestinal stem cells is supported by a niche which is composed of several signaling proteins including the Hippo pathway effectors YAP1/TAZ. The role of YAP1/TAZ in cell proliferation and regeneration is well documented but their involvement on the differentiation of intestinal epithelial cells is unclear. In the present study, the role of YAP1/TAZ on the differentiation of intestinal epithelial cells was investigated using the HT29 cell line, the only multipotent intestinal cell line available, with a combination of knockdown approaches. The expression of intestinal differentiation cell markers was tested by qPCR, Western blot, indirect immunofluorescence and electron microscopy analyses. The results show that TAZ is not expressed while the abolition of YAP1 expression led to a sharp increase in goblet and absorptive cell differentiation and reduction of some stem cell markers. Further studies using double knockdown experiments revealed that most of these effects resulting from YAP1 abolition are mediated by CDX2, a key intestinal cell transcription factor. In conclusion, our results indicate that YAP1/TAZ negatively regulate the differentiation of intestinal epithelial cells through the inhibition of CDX2 expression.https://www.mdpi.com/2073-4409/9/8/1895Hippo pathwayYAP1TAZintestinal celldifferentiationCDX2 |
| spellingShingle | Sepideh Fallah Jean-François Beaulieu The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation Cells Hippo pathway YAP1 TAZ intestinal cell differentiation CDX2 |
| title | The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation |
| title_full | The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation |
| title_fullStr | The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation |
| title_full_unstemmed | The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation |
| title_short | The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation |
| title_sort | hippo pathway effector yap1 regulates intestinal epithelial cell differentiation |
| topic | Hippo pathway YAP1 TAZ intestinal cell differentiation CDX2 |
| url | https://www.mdpi.com/2073-4409/9/8/1895 |
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