Epithelial-Mesenchymal Micro-niches Govern Stem Cell Lineage Choices

Cell. 2017 Apr 20;169(3):483-496.e13. doi: 10.1016/j.cell.2017.03.038. Epub 2017 Apr 13.


Adult tissue stem cells (SCs) reside in niches, which, through intercellular contacts and signaling, influence SC behavior. Once activated, SCs typically give rise to short-lived transit-amplifying cells (TACs), which then progress to differentiate into their lineages. Here, using single-cell RNA-seq, we unearth unexpected heterogeneity among SCs and TACs of hair follicles. We trace the roots of this heterogeneity to micro-niches along epithelial-mesenchymal interfaces, where progenitors display molecular signatures reflective of spatially distinct local signals and intercellular interactions. Using lineage tracing, temporal single-cell analyses, and chromatin landscaping, we show that SC plasticity becomes restricted in a sequentially and spatially choreographed program, culminating in seven spatially arranged unilineage progenitors within TACs of mature follicles. By compartmentalizing SCs into micro-niches, tissues gain precise control over morphogenesis and regeneration: some progenitors specify lineages immediately, whereas others retain potency, preserving self-renewing features established early while progressively restricting lineages as they experience dynamic changes in microenvironment.

Keywords: epithelial-mesenchymal interactions; lineage determination; single-cell analyses; stem cells; tissue regeneration.

Publication types

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

MeSH terms

  • Adult Stem Cells / cytology*
  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • Cell Lineage*
  • Hair Follicle / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Stem Cell Niche*
  • Wnt Signaling Pathway


  • Bone Morphogenetic Proteins