Mesenchymal Hippo signaling regulates intestinal homeostasis in adult mice
Summary: Intestinal homeostasis is tightly regulated by the reciprocal interaction between the gut epithelium and adjacent mesenchyme. The Hippo pathway is intimately associated with intestinal epithelial homeostasis and regeneration; however, its role in postnatal gut mesenchyme remains poorly defi...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001075 |
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| author | Kyvan Dang Alka Singh Xin Chen Jennifer L. Cotton Susu Guo Xiaodi Hu Zhipeng Tao Haibo Liu Lihua J. Zhu Y. Tony Ip Xu Wu Junhao Mao |
| author_facet | Kyvan Dang Alka Singh Xin Chen Jennifer L. Cotton Susu Guo Xiaodi Hu Zhipeng Tao Haibo Liu Lihua J. Zhu Y. Tony Ip Xu Wu Junhao Mao |
| author_sort | Kyvan Dang |
| collection | DOAJ |
| description | Summary: Intestinal homeostasis is tightly regulated by the reciprocal interaction between the gut epithelium and adjacent mesenchyme. The Hippo pathway is intimately associated with intestinal epithelial homeostasis and regeneration; however, its role in postnatal gut mesenchyme remains poorly defined. Here, we find that removal of the core Hippo kinases Lats1/2 or activation of YAP in adult intestinal smooth muscle layers has largely no effect; however, Hippo-YAP signaling in the niche-forming Gli1+ mesenchymal cells plays intrinsic roles in regulating intestinal homeostasis. We find that Lats1/2 deletion drives robust mesenchymal over-proliferation, and YAP activation in Gli1+ pericryptal cells disrupts the intestinal epithelial-mesenchymal crosstalk via promoting Wnt ligand production. We show that YAP is upregulated in the stroma during dextran sodium sulfate (DSS)-induced injury, and mesenchymal YAP activation facilitates intestinal epithelial regeneration. Altogether, our data suggest an important role for mesenchymal Hippo-YAP signaling in the stem cell niche during intestinal homeostasis and pathogenesis. |
| format | Article |
| id | doaj-art-5fbfe4c54ff845e7b24ed7df1534d026 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-5fbfe4c54ff845e7b24ed7df1534d0262025-02-02T05:29:10ZengElsevieriScience2589-00422025-02-01282111847Mesenchymal Hippo signaling regulates intestinal homeostasis in adult miceKyvan Dang0Alka Singh1Xin Chen2Jennifer L. Cotton3Susu Guo4Xiaodi Hu5Zhipeng Tao6Haibo Liu7Lihua J. Zhu8Y. Tony Ip9Xu Wu10Junhao Mao11Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USADepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USADepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USADepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USADepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USADepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USACutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Nutrition and Food Sciences, Texas Woman’s University, Denton, TX 76204, USADepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USADepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USACutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USADepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Corresponding authorSummary: Intestinal homeostasis is tightly regulated by the reciprocal interaction between the gut epithelium and adjacent mesenchyme. The Hippo pathway is intimately associated with intestinal epithelial homeostasis and regeneration; however, its role in postnatal gut mesenchyme remains poorly defined. Here, we find that removal of the core Hippo kinases Lats1/2 or activation of YAP in adult intestinal smooth muscle layers has largely no effect; however, Hippo-YAP signaling in the niche-forming Gli1+ mesenchymal cells plays intrinsic roles in regulating intestinal homeostasis. We find that Lats1/2 deletion drives robust mesenchymal over-proliferation, and YAP activation in Gli1+ pericryptal cells disrupts the intestinal epithelial-mesenchymal crosstalk via promoting Wnt ligand production. We show that YAP is upregulated in the stroma during dextran sodium sulfate (DSS)-induced injury, and mesenchymal YAP activation facilitates intestinal epithelial regeneration. Altogether, our data suggest an important role for mesenchymal Hippo-YAP signaling in the stem cell niche during intestinal homeostasis and pathogenesis.http://www.sciencedirect.com/science/article/pii/S2589004225001075Molecular biologyCell biology |
| spellingShingle | Kyvan Dang Alka Singh Xin Chen Jennifer L. Cotton Susu Guo Xiaodi Hu Zhipeng Tao Haibo Liu Lihua J. Zhu Y. Tony Ip Xu Wu Junhao Mao Mesenchymal Hippo signaling regulates intestinal homeostasis in adult mice iScience Molecular biology Cell biology |
| title | Mesenchymal Hippo signaling regulates intestinal homeostasis in adult mice |
| title_full | Mesenchymal Hippo signaling regulates intestinal homeostasis in adult mice |
| title_fullStr | Mesenchymal Hippo signaling regulates intestinal homeostasis in adult mice |
| title_full_unstemmed | Mesenchymal Hippo signaling regulates intestinal homeostasis in adult mice |
| title_short | Mesenchymal Hippo signaling regulates intestinal homeostasis in adult mice |
| title_sort | mesenchymal hippo signaling regulates intestinal homeostasis in adult mice |
| topic | Molecular biology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001075 |
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