Stem cells repurpose proliferation to contain a breach in their niche barrier

Elife. 2018 Dec 6:7:e41661. doi: 10.7554/eLife.41661.

Abstract

Adult stem cells are responsible for life-long tissue maintenance. They reside in and interact with specialized tissue microenvironments (niches). Using murine hair follicle as a model, we show that when junctional perturbations in the niche disrupt barrier function, adjacent stem cells dramatically change their transcriptome independent of bacterial invasion and become capable of directly signaling to and recruiting immune cells. Additionally, these stem cells elevate cell cycle transcripts which reduce their quiescence threshold, enabling them to selectively proliferate within this microenvironment of immune distress cues. However, rather than mobilizing to fuel new tissue regeneration, these ectopically proliferative stem cells remain within their niche to contain the breach. Together, our findings expose a potential communication relay system that operates from the niche to the stem cells to the immune system and back. The repurposing of proliferation by these stem cells patch the breached barrier, stoke the immune response and restore niche integrity.

Keywords: Regulatory T cells; cell-cell adhesion; immune-stem cell interactions; mouse; regenerative medicine; sensing tissue damage; stem cell signaling; stem cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Communication / genetics
  • Cell Cycle / genetics
  • Cell Proliferation / genetics*
  • Cells, Cultured
  • Gene Expression Profiling / methods*
  • Hair Follicle / cytology
  • Hair Follicle / metabolism*
  • Hair Follicle / ultrastructure
  • Homeostasis / genetics
  • Humans
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Stem Cell Niche*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stem Cells / ultrastructure