title: Ezh2 represses the basal cell lineage during lung endoderm development.
abstract: The development of the lung epithelium is regulated in a stepwise fashion to generate numerous differentiated and stem cell lineages in the adult lung. How these different lineages are generated in a spatially and temporally restricted fashion remains poorly understood, although epigenetic regulation probably plays an important role. We show that the Polycomb repressive complex 2 component Ezh2 is highly expressed in early lung development but is gradually downregulated by late gestation. Deletion of Ezh2 in early lung endoderm progenitors leads to the ectopic and premature appearance of Trp63+ basal cells that extend the entire length of the airway. Loss of Ezh2 also leads to reduced secretory cell differentiation. In their place, morphologically similar cells develop that express a subset of basal cell genes, including keratin 5, but no longer express high levels of either Trp63 or of standard secretory cell markers. This suggests that Ezh2 regulates the phenotypic switch between basal cells and secretory cells. Together, these findings show that Ezh2 restricts the basal cell lineage during normal lung endoderm development to allow the proper patterning of epithelial lineages during lung formation.
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Snitow
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Shanru
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Morley
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Komal
authors.initials: K
authors.lastname: Rathi
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Min Min
authors.initials: MM
authors.lastname: Lu
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Kadzik
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Stewart
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA emorrise@mail.med.upenn.edu.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Morrisey
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D004707:Endoderm / Q000166:cytology* / Q000196:embryology*; D000071221:Enhancer of Zeste Homolog 2 Protein; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D063990:Gene Ontology; D020397:Goblet Cells / Q000166:cytology / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D053555:Keratin-5 / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D055099:Neuroendocrine Cells / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D012984:Software; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053823:Hedgehog Proteins; D053555:Keratin-5; D009687:Nuclear Proteins; D010750:Phosphoproteins; C465570:Shh protein, mouse; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2
keywords: Basal cell; Endoderm; Lung; Mouse