title: Ezh2 restricts the smooth muscle lineage during mouse lung mesothelial development.
abstract: During development, the lung mesoderm generates a variety of cell lineages, including airway and vascular smooth muscle. Epigenetic changes in adult lung mesodermal lineages are thought to contribute towards diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, although the factors that regulate early lung mesoderm development are unknown. We show in mouse that the PRC2 component Ezh2 is required to restrict smooth muscle differentiation in the developing lung mesothelium. Mesodermal loss of Ezh2 leads to the formation of ectopic smooth muscle in the submesothelial region of the developing lung mesoderm. Loss of Ezh2 specifically in the developing mesothelium reveals a mesothelial cell-autonomous role for Ezh2 in repression of the smooth muscle differentiation program. Loss of Ezh2 derepresses expression of myocardin and Tbx18, which are important regulators of smooth muscle differentiation from the mesothelium and related cell lineages. Together, these findings uncover an Ezh2-dependent mechanism to restrict the smooth muscle gene expression program in the developing mesothelium and allow appropriate cell fate decisions to occur in this multipotent mesoderm lineage.
authors: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.|Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.|Penn Center for Pulmonary Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.|Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Melinda
authors: M
authors: Snitow
authors: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.|Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: MinMin
authors: M
authors: Lu
authors: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.|Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Lan
authors: L
authors: Cheng
authors: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.|Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Su
authors: S
authors: Zhou
authors: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA emorrise@mail.med.upenn.edu.|Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.|Penn Center for Pulmonary Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.|Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.|Penn Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Edward E
authors: 0000-0001-5785-1939
authors: EE
authors: Morrisey
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology* / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000099251:Myocardin
chemical_list: D000071221:Enhancer of Zeste Homolog 2 Protein; D009687:Nuclear Proteins; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D000099251:Myocardin; C420983:Tbx18 protein, mouse; C498410:Ezh2 protein, mouse
keywords: Ezh2; Lung development; Mesoderm; Mesothelium; Polycomb repressive complex 2; Smooth muscle