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...

Full description

Saved in:
Bibliographic Details
Published in:Cell 2017-09, Vol.170 (6), p.1149-1163.e12
Main Authors: Lee, Joo-Hyeon, Tammela, Tuomas, Hofree, Matan, Choi, Jinwook, Marjanovic, Nemanja Despot, Han, Seungmin, Canner, David, Wu, Katherine, Paschini, Margherita, Bhang, Dong Ha, Jacks, Tyler, Regev, Aviv, Kim, Carla F.
Format: Article
Language:English
Subjects:
alveolar epithelium
Animals
bronchiolar epithelium
differentiation
Homeostasis
lung
Lung - cytology
Lung - physiology
lung stem cells
mesenchymal cells
Mesoderm - cytology
Mice
niche
Organoids - cytology
Pulmonary Alveoli - cytology
Receptors, G-Protein-Coupled - analysis
Sequence Analysis, RNA
Single-Cell Analysis
Transcription, Genetic
Wnt signaling
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. [Display omitted] •Lgr5 and Lgr6 mark mesenchymal cells in adult lungs•Single-cell transcriptome analysis defines mesenchymal heterogeneity•Distinct mesenchymal niches drive airway and alveolar differentiation•Wnt activity affects epithelial differentiation specified by mesenchymal cells Heterogeneous mesenchymal cell populations in the lung play a central role in epithelial maintenance and alveolar differentiation.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2017.07.028