Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6
The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissue...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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Elsevier BV
2018
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| Online Access: | http://hdl.handle.net/1721.1/116555 https://orcid.org/0000-0003-3675-6961 https://orcid.org/0000-0002-0060-7131 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0001-8567-2049 |
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| author | Lee, Joo-Hyeon Hofree, Matan Choi, Jinwook Han, Seungmin Paschini, Margherita Bhang, Dong Ha Kim, Carla F. Tammela, Tuomas Marjanovic, Nemanja Canner, David Allen Wu, Katherine Jacks, Tyler E. Regev, Aviv |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Lee, Joo-Hyeon Hofree, Matan Choi, Jinwook Han, Seungmin Paschini, Margherita Bhang, Dong Ha Kim, Carla F. Tammela, Tuomas Marjanovic, Nemanja Canner, David Allen Wu, Katherine Jacks, Tyler E. Regev, Aviv |
| author_sort | Lee, Joo-Hyeon |
| collection | MIT |
| description | The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissues, are markers of mesenchymal cells in the adult lung. Lgr6 + cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia and promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation. Genetic ablation of Lgr6 + cells impairs airway injury repair in vivo. Distinct Lgr5 + cells are located in alveolar compartments and are sufficient to promote alveolar differentiation of epithelial progenitors through Wnt activation. Modulating Wnt activity altered differentiation outcomes specified by mesenchymal cells. This identification of region- and lineage-specific crosstalk between epithelium and their neighboring mesenchymal partners provides new understanding of how different cell types are maintained in the adult lung. Keywords:
mesenchymal cells; bronchiolar epithelium; alveolar epithelium;
lung stem cells; lung; differentiation; niche; Wnt signaling |
| first_indexed | 2024-09-23T12:43:32Z |
| format | Article |
| id | mit-1721.1/116555 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T12:43:32Z |
| publishDate | 2018 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1165552022-09-28T09:42:12Z Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6 Lee, Joo-Hyeon Hofree, Matan Choi, Jinwook Han, Seungmin Paschini, Margherita Bhang, Dong Ha Kim, Carla F. Tammela, Tuomas Marjanovic, Nemanja Canner, David Allen Wu, Katherine Jacks, Tyler E. Regev, Aviv Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Tammela, Tuomas Marjanovic, Nemanja Canner, David Allen Wu, Katherine Jacks, Tyler E. Regev, Aviv The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissues, are markers of mesenchymal cells in the adult lung. Lgr6 + cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia and promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation. Genetic ablation of Lgr6 + cells impairs airway injury repair in vivo. Distinct Lgr5 + cells are located in alveolar compartments and are sufficient to promote alveolar differentiation of epithelial progenitors through Wnt activation. Modulating Wnt activity altered differentiation outcomes specified by mesenchymal cells. This identification of region- and lineage-specific crosstalk between epithelium and their neighboring mesenchymal partners provides new understanding of how different cell types are maintained in the adult lung. Keywords: mesenchymal cells; bronchiolar epithelium; alveolar epithelium; lung stem cells; lung; differentiation; niche; Wnt signaling 2018-06-25T14:58:01Z 2018-06-25T14:58:01Z 2017-09 2017-06 2018-06-25T14:13:25Z Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/116555 Lee, Joo-Hyeon et al. “Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6.” Cell 170, 6 (September 2017): 1149–1163 © 2017 The Authors https://orcid.org/0000-0003-3675-6961 https://orcid.org/0000-0002-0060-7131 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0001-8567-2049 http://dx.doi.org/10.1016/J.CELL.2017.07.028 Cell Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Lee, Joo-Hyeon Hofree, Matan Choi, Jinwook Han, Seungmin Paschini, Margherita Bhang, Dong Ha Kim, Carla F. Tammela, Tuomas Marjanovic, Nemanja Canner, David Allen Wu, Katherine Jacks, Tyler E. Regev, Aviv Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6 |
| title | Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6 |
| title_full | Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6 |
| title_fullStr | Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6 |
| title_full_unstemmed | Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6 |
| title_short | Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6 |
| title_sort | anatomically and functionally distinct lung mesenchymal populations marked by lgr5 and lgr6 |
| url | http://hdl.handle.net/1721.1/116555 https://orcid.org/0000-0003-3675-6961 https://orcid.org/0000-0002-0060-7131 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0001-8567-2049 |
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