Format

Send to

Choose Destination
Cell. 2017 Sep 7;170(6):1149-1163.e12. doi: 10.1016/j.cell.2017.07.028.

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

Author information

1
Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK. Electronic address: jhl62@cam.ac.uk.
2
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
3
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
4
Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
5
Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
6
Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
7
Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
8
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
9
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
10
Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: carla.kim@childrens.harvard.edu.

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:

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

PMID:
28886383
PMCID:
PMC5607351
DOI:
10.1016/j.cell.2017.07.028
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center