Yap tunes airway epithelial size and architecture by regulating the identity, maintenance, and self-renewal of stem cells

Dev Cell. 2014 Jul 28;30(2):151-65. doi: 10.1016/j.devcel.2014.06.004. Epub 2014 Jul 17.

Abstract

Our understanding of how stem cells are regulated to maintain appropriate tissue size and architecture is incomplete. We show that Yap (Yes-associated protein 1) is required for the actual maintenance of an adult mammalian stem cell. Without Yap, adult airway basal stem cells are lost through their unrestrained differentiation, resulting in the simplification of a pseudostratified epithelium into a columnar one. Conversely, Yap overexpression increases stem cell self-renewal and blocks terminal differentiation, resulting in epithelial hyperplasia and stratification. Yap overexpression in differentiated secretory cells causes them to partially reprogram and adopt a stem cell-like identity. In contrast, Yap knockdown prevents the dedifferentiation of secretory cells into stem cells. We then show that Yap functionally interacts with p63, the cardinal transcription factor associated with myriad epithelial basal stem cells. In aggregate, we show that Yap regulates all of the cardinal behaviors of airway epithelial stem cells and determines epithelial architecture.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism
  • Animals
  • Cell Cycle Proteins
  • Cell Differentiation*
  • Cell Proliferation*
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Mice
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Trachea / cytology*
  • Trachea / metabolism
  • Trans-Activators / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Phosphoproteins
  • Trans-Activators
  • Trp63 protein, mouse
  • Yap protein, mouse