JAG1-Mediated Notch Signaling Regulates Secretory Cell Differentiation of the Human Airway Epithelium

Stem Cell Rev Rep. 2016 Aug;12(4):454-63. doi: 10.1007/s12015-016-9656-6.

Abstract

Basal cells (BC) are the stem/progenitor cells of the human airway epithelium capable of differentiating into secretory and ciliated cells. Notch signaling activation increases BC differentiation into secretory cells, but the role of individual Notch ligands in regulating this process in the human airway epithelium is largely unknown. The objective of this study was to define the role of the Notch ligand JAG1 in regulating human BC differentiation. JAG1 over-expression in BC increased secretory cell differentiation, with no effect on ciliated cell differentiation. Conversely, knockdown of JAG1 decreased expression of secretory cell genes. These data demonstrate JAG1-mediated Notch signaling regulates differentiation of BC into secretory cells.

Keywords: Basal stem/progenitor cells; Differentiation; Human airway epithelium; JAG1; Notch signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Blotting, Western
  • Cell Differentiation / genetics*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelium / metabolism*
  • Fluorescent Antibody Technique
  • Gene Expression Profiling / methods
  • Humans
  • Jagged-1 Protein / genetics*
  • Jagged-1 Protein / metabolism
  • RNA Interference
  • Receptors, Notch / genetics*
  • Receptors, Notch / metabolism
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, RNA / methods
  • Signal Transduction / genetics*
  • Stem Cells / cytology
  • Stem Cells / metabolism

Substances

  • JAG1 protein, human
  • Jagged-1 Protein
  • Receptors, Notch