β-catenin maintains lung epithelial progenitors after lung specification

Edwin J. Ostrin, Danielle R. Little, Kamryn N. Gerner-Mauro, Elizabeth A. Sumner, Ricardo Rı́os-Corzo, Elizabeth Ambrosio, Samantha E. Holt, Nicolas Forcioli-Conti, Haruhiko Akiyama, Sam M. Hanash, Shioko Kimura, Sarah X.L. Huang, Jichao Chen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The entire lung epithelium arises from SRY box 9 (SOX9)-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, progenitorspecific genetic mosaic mouse models, we showed that β-catenin (CTNNB1) maintains lung progenitors by promoting a hierarchical lung progenitor gene signature, suppressing gastrointestinal (GI) genes, and regulating NK2 homeobox 1 (NKX2.1) and SRY box 2 (SOX2) in a developmental stage-dependent manner. At the early, but not later, stage post-lung specification, CTNNB1 cell-autonomously maintained normal NKX2.1 expression levels and suppressed ectopic SOX2 expression. Genetic epistasis analyses revealed that CTNNB1 is required for fibroblast growth factor (Fgf)/Kirsten rat sarcoma viral oncogene homolog (Kras)-mediated promotion of the progenitors. In silico screening of Eurexpress and translating ribosome affinity purification (TRAP)-RNAseq identified a progenitor gene signature, a subset of which depends on CTNNB1. Wnt signaling also maintained NKX2.1 expression and suppressed GI genes in cultured human lung progenitors derived from embryonic stem cells.

Original languageEnglish (US)
Article numberdev160788
JournalDevelopment (Cambridge)
Volume145
Issue number5
DOIs
StatePublished - Mar 2018

Fingerprint

Catenins
Lung
Genes
Genetic Epistasis
Alveolar Epithelial Cells
Fibroblast Growth Factors
Homeobox Genes
Embryonic Stem Cells
Ribosomes
Oncogenes
Sarcoma
Computer Simulation
Epithelium

Keywords

  • Beta-catenin
  • Epithelial progenitors
  • Lung development
  • Mouse

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Ostrin, E. J., Little, D. R., Gerner-Mauro, K. N., Sumner, E. A., Rı́os-Corzo, R., Ambrosio, E., ... Chen, J. (2018). β-catenin maintains lung epithelial progenitors after lung specification. Development (Cambridge), 145(5), [dev160788]. https://doi.org/10.1242/dev.160788

β-catenin maintains lung epithelial progenitors after lung specification. / Ostrin, Edwin J.; Little, Danielle R.; Gerner-Mauro, Kamryn N.; Sumner, Elizabeth A.; Rı́os-Corzo, Ricardo; Ambrosio, Elizabeth; Holt, Samantha E.; Forcioli-Conti, Nicolas; Akiyama, Haruhiko; Hanash, Sam M.; Kimura, Shioko; Huang, Sarah X.L.; Chen, Jichao.

In: Development (Cambridge), Vol. 145, No. 5, dev160788, 03.2018.

Research output: Contribution to journalArticle

Ostrin, EJ, Little, DR, Gerner-Mauro, KN, Sumner, EA, Rı́os-Corzo, R, Ambrosio, E, Holt, SE, Forcioli-Conti, N, Akiyama, H, Hanash, SM, Kimura, S, Huang, SXL & Chen, J 2018, 'β-catenin maintains lung epithelial progenitors after lung specification', Development (Cambridge), vol. 145, no. 5, dev160788. https://doi.org/10.1242/dev.160788
Ostrin EJ, Little DR, Gerner-Mauro KN, Sumner EA, Rı́os-Corzo R, Ambrosio E et al. β-catenin maintains lung epithelial progenitors after lung specification. Development (Cambridge). 2018 Mar;145(5). dev160788. https://doi.org/10.1242/dev.160788
Ostrin, Edwin J. ; Little, Danielle R. ; Gerner-Mauro, Kamryn N. ; Sumner, Elizabeth A. ; Rı́os-Corzo, Ricardo ; Ambrosio, Elizabeth ; Holt, Samantha E. ; Forcioli-Conti, Nicolas ; Akiyama, Haruhiko ; Hanash, Sam M. ; Kimura, Shioko ; Huang, Sarah X.L. ; Chen, Jichao. / β-catenin maintains lung epithelial progenitors after lung specification. In: Development (Cambridge). 2018 ; Vol. 145, No. 5.
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