Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning
Abstract Intestinal epithelial cells are segregated into proliferative crypts and differentiated regions. This organization relies on specific signals, including Wnt3a, which regulates cell proliferation within crypts, and Eph/Ephrin, which dictates cell positioning along the crypt-villus axis. Howe...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55651-7 |
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| author | Enara Larrañaga Miquel Marin-Riera Aina Abad-Lázaro David Bartolomé-Català Aitor Otero Vanesa Fernández-Majada Eduard Batlle James Sharpe Samuel Ojosnegros Jordi Comelles Elena Martinez |
| author_facet | Enara Larrañaga Miquel Marin-Riera Aina Abad-Lázaro David Bartolomé-Català Aitor Otero Vanesa Fernández-Majada Eduard Batlle James Sharpe Samuel Ojosnegros Jordi Comelles Elena Martinez |
| author_sort | Enara Larrañaga |
| collection | DOAJ |
| description | Abstract Intestinal epithelial cells are segregated into proliferative crypts and differentiated regions. This organization relies on specific signals, including Wnt3a, which regulates cell proliferation within crypts, and Eph/Ephrin, which dictates cell positioning along the crypt-villus axis. However, studying how the spatial distributions of these signals influences crypt-villus organization is challenging both in vitro and in vivo. Here we show that micropatterns of Wnt3a can govern the size, shape and long-range organization of crypts in vitro. By adjusting the spacing between Wnt3a ligand patterns at the microscale over large surfaces, we override endogenous Wnt3a to precisely control the distribution and long-range order of crypt-like regions in primary epithelial monolayers. Additionally, an agent-based model integrating Wnt3a/BMP feedback and Eph/Ephrin repulsion effectively replicates experimental tissue compartmentalization, crypt size, shape, and organization. This combined experimental and computational approach offers a framework to study how signaling pathways help organize intestinal epithelial tissue. |
| format | Article |
| id | doaj-art-d8e3b729889d442487c3ccfbd0f59c04 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d8e3b729889d442487c3ccfbd0f59c042025-01-05T12:38:05ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-024-55651-7Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterningEnara Larrañaga0Miquel Marin-Riera1Aina Abad-Lázaro2David Bartolomé-Català3Aitor Otero4Vanesa Fernández-Majada5Eduard Batlle6James Sharpe7Samuel Ojosnegros8Jordi Comelles9Elena Martinez10Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST)European Molecular Biology Laboratory (EMBL)Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST)Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST)Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST)Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST)Institute for Research in Biomedicine (IRB), The Barcelona Institute of Science and Technology (BIST)European Molecular Biology Laboratory (EMBL)Bioengineering in Reproductive Health, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST)Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST)Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST)Abstract Intestinal epithelial cells are segregated into proliferative crypts and differentiated regions. This organization relies on specific signals, including Wnt3a, which regulates cell proliferation within crypts, and Eph/Ephrin, which dictates cell positioning along the crypt-villus axis. However, studying how the spatial distributions of these signals influences crypt-villus organization is challenging both in vitro and in vivo. Here we show that micropatterns of Wnt3a can govern the size, shape and long-range organization of crypts in vitro. By adjusting the spacing between Wnt3a ligand patterns at the microscale over large surfaces, we override endogenous Wnt3a to precisely control the distribution and long-range order of crypt-like regions in primary epithelial monolayers. Additionally, an agent-based model integrating Wnt3a/BMP feedback and Eph/Ephrin repulsion effectively replicates experimental tissue compartmentalization, crypt size, shape, and organization. This combined experimental and computational approach offers a framework to study how signaling pathways help organize intestinal epithelial tissue.https://doi.org/10.1038/s41467-024-55651-7 |
| spellingShingle | Enara Larrañaga Miquel Marin-Riera Aina Abad-Lázaro David Bartolomé-Català Aitor Otero Vanesa Fernández-Majada Eduard Batlle James Sharpe Samuel Ojosnegros Jordi Comelles Elena Martinez Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning Nature Communications |
| title | Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning |
| title_full | Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning |
| title_fullStr | Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning |
| title_full_unstemmed | Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning |
| title_short | Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning |
| title_sort | long range organization of intestinal 2d crypts using exogenous wnt3a micropatterning |
| url | https://doi.org/10.1038/s41467-024-55651-7 |
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