Myb permits multilineage airway epithelial cell differentiation

Jie Hong Pan, Tracy L. Adair-Kirk, Anand C. Patel, Tao Huang, Nicholas S. Yozamp, Jian Xu, E. Premkumar Reddy, Derek E. Byers, Richard A. Pierce, Michael J. Holtzman, Steven L. Brody

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The epithelium of the pulmonary airway is specially differentiated to provide defense against environmental insults, but also subject to dysregulated differentiation that results in lung disease. The current paradigm for airway epithelial differentiation is a one-step program whereby a p63+ basal epithelial progenitor cell generates a ciliated or secretory cell lineage, but the cue for this transition and whether there are intermediate steps are poorly defined. Here, we identify transcription factor Myb as a key regulator that permits early multilineage differentiation of airway epithelial cells. Myb+ cells were identified as p63- and therefore distinct from basal progenitor cells, but were still negative for markers of differentiation. Myb RNAi treatment of primary-culture airway epithelial cells and Myb gene deletion in mice resulted in a p63- population with failed maturation of Foxj1+ ciliated cells as well as Scbg1a1+ and Muc5ac+ secretory cells. Consistent with these findings, analysis of whole genome expression of Myb-deficient cells identified Myb-dependent programs for ciliated and secretory cell differentiation. Myb+ cells were rare in human airways but were increased in regions of ciliated cells and mucous cell hyperplasia in samples from subjects with chronic obstructive pulmonary disease. Together, the results show that a p63- Myb+ population of airway epithelial cells represents a distinct intermediate stage of differentiation that is required under normal conditions and may be heightened in airway disease. Stem Cells 2014;32:3245-3256

Original languageEnglish
Pages (from-to)3245-3256
Number of pages12
JournalSTEM CELLS
Volume32
Issue number12
DOIs
StatePublished - Dec 1 2014

Keywords

  • Cell lineage
  • Cells
  • Chronic obstructive
  • Cilia
  • Cultured
  • Pulmonary disease
  • Respiratory system
  • Secretoglobins

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