Open AccessBeta-Catenin maintains lung epithelial progenitors after lung specification
Author(s) -
Edwin J. Ostrin,
Danielle R. Little,
Kamryn N. Gerner-Mauro,
Elizabeth Sumner,
Ricardo Ríos-Corzo,
Elizabeth Mayela Ambrosio,
Samantha E. Holt,
Nicolas R. Forcioli-Conti,
Haruhiko Akiyama,
Sam Hanash,
Shioko Kimura,
Sarah X.L. Huang,
Jichao Chen
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.160788
Subject(s) - biology , progenitor cell , sox2 , embryonic stem cell , progenitor , ectopic expression , wnt signaling pathway , microbiology and biotechnology , stem cell , cancer research , immunology , genetics , gene , signal transduction
The entire lung epithelium arises from SOX9 (SRY box 9)-expressing progenitors that form the respiratory tree and differentiate into airway and alveolar cells. Despite progress in understanding their initial specification within the embryonic foregut, how these progenitors are subsequently maintained is less clear. Using inducible, progenitor-specific genetic mosaic mouse models, we show that beta-Catenin (CTNNB1) maintains the lung progenitors by promoting a hierarchical lung progenitor gene signature, suppressing gastrointestinal (GI) genes, and regulating NKX2.1 (NK2 homeobox 1) and SOX2 (SRY box 2) in a developmental stage dependent manner. At the early, but not later, stage post lung specification, CTNNB1 cell-autonomously maintains the normal NKX2.1 expression level and suppresses ectopic SOX2 expression. Genetic epistasis analyses reveal that CTNNB1 is required for Fgf (fibroblast growth factor)/Kras (Kirsten rat sarcoma viral oncogene homolog)-mediated promotion of the progenitors. In silico screening of Eurexpress and TRAP (translating ribosome affinity purification)-RNAseq identify a progenitor gene signature, a subset of which depends on CTNNB1. Wnt signaling also maintains NKX2.1 expression and suppresses GI genes in cultured human lung progenitors that are derived from embryonic stem cells.