GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells.

Published

Journal Article

Pseudostratified airway epithelium of the lung is composed of polarized ciliated and secretory cells maintained by basal stem/progenitor cells. An important question is how lineage choice and differentiation are coordinated with apical-basal polarity and epithelial morphogenesis. Our previous studies indicated a key integrative role for the transcription factor Grainyhead-like 2 (Grhl2). In this study, we present further evidence for this model using conditional gene deletion during the regeneration of airway epithelium and clonal organoid culture. We also use CRISPR/Cas9 genome editing in primary human basal cells differentiating into organoids and mucociliary epithelium in vitro. Loss of Grhl2 inhibits organoid morphogenesis and the differentiation of ciliated cells and reduces the expression of both notch and ciliogenesis genes (Mcidas, Rfx2, and Myb) with distinct Grhl2 regulatory sites. The genome editing of other putative target genes reveals roles for zinc finger transcription factor Znf750 and small membrane adhesion glycoprotein in promoting ciliogenesis and barrier function as part of a network of genes coordinately regulated by Grhl2.

Full Text

Duke Authors

Cited Authors

  • Gao, X; Bali, AS; Randell, SH; Hogan, BLM

Published Date

  • November 9, 2015

Published In

Volume / Issue

  • 211 / 3

Start / End Page

  • 669 - 682

PubMed ID

  • 26527742

Pubmed Central ID

  • 26527742

Electronic International Standard Serial Number (EISSN)

  • 1540-8140

Digital Object Identifier (DOI)

  • 10.1083/jcb.201506014

Language

  • eng

Conference Location

  • United States