Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6

Joo Hyeon Lee*, Tuomas Tammela, Matan Hofree, Jinwook Choi, Nemanja Despot Marjanovic, Seungmin Han, David Canner, Katherine Wu, Margherita Paschini, Dong Ha Bhang, Tyler Jacks, Aviv Regev, Carla F. Kim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

249 Scopus citations

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.

Original languageAmerican English
Pages (from-to)1149-1163.e12
JournalCell
Volume170
Issue number6
DOIs
StatePublished - 7 Sep 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 The Authors

Keywords

  • Wnt signaling
  • alveolar epithelium
  • bronchiolar epithelium
  • differentiation
  • lung
  • lung stem cells
  • mesenchymal cells
  • niche

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