β-Catenin maintains lung epithelial progenitors after lung specification.

Autor:	Ostrin EJ; Department of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.; Department of General Internal Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Little DR; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, Texas 77030, USA., Gerner-Mauro KN; Department of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Sumner EA; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, Texas 77030, USA., Ríos-Corzo R; School of Medicine and Health Sciences, Tecnológico de Monterrey, Monterrey, Nuevo León 64849, Mexico., Ambrosio E; School of Engineering and Sciences, Tecnológico de Monterrey, Monterrey, Nuevo León 64849, Mexico., Holt SE; Department of Clinical Cancer Prevention, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Forcioli-Conti N; Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, the University of Texas Health Science Center at Houston, Houston, Texas 77030, USA., Akiyama H; Department of Orthopedics, Kyoto University, Sakyo, Kyoto 606-8507, Japan., Hanash SM; Department of Clinical Cancer Prevention, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Kimura S; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Huang SXL; Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, the University of Texas Health Science Center at Houston, Houston, Texas 77030, USA., Chen J; Department of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA jchen16@mdanderson.org.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2018 Mar 09; Vol. 145 (5). Date of Electronic Publication: 2018 Mar 09.
DOI:	10.1242/dev.160788
Abstrakt:	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, progenitor-specific 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. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2018. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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