Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6
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1-s2.0-S0092867417308644-main.pdf
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Author(s)
Lee, Joo-Hyeon
Hofree, Matan
Choi, Jinwook
Han, Seungmin
Paschini, Margherita
Bhang, Dong Ha
Kim, Carla F.
Tammela, Tuomas
Marjanovic, Nemanja
Canner, David Allen
Date Issued
September 2017
Journal
Cell
Publisher
Elsevier BV
Citation
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
Version
Final published version
Abstract
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
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1016/J.CELL.2017.07.028
