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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2017 Sep 9

PMID 28886383

Citations 206

Authors

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

Affiliations

Soon will be listed here.

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.

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