Hair Follicle Terminal Differentiation Is Orchestrated by Distinct Early and Late Matrix Progenitors

Cell Rep. 2017 Apr 25;19(4):809-821. doi: 10.1016/j.celrep.2017.03.077.

Abstract

During development and regeneration, matrix progenitors undergo terminal differentiation to form the concentric layers of the hair follicle. These differentiation events are thought to require signals from the mesenchymal dermal papilla (DP); however, it remains unclear how DP-progenitor cell interactions govern specific cell fate decisions. Here, we show that the hair follicle differentiated layers are specified asynchronously, with early matrix progenitors initiating differentiation before surrounding the DP. Furthermore, these early matrix cells can undergo terminal differentiation in the absence of Shh, BMP signaling, and DP maturation. Whereas early matrix progenitors form the hair follicle companion layer, later matrix populations progressively form the inner root sheath and hair shaft. Altogether, our findings characterize some of the earliest terminal differentiation events in the hair follicle and reveal that the matrix progenitor pool can be divided into early and late phases based on distinct temporal, molecular, and functional characteristics.

Keywords: companion layer; hair cycle; hair follicle stem cells; inner root sheath; keratin 79; matrix cell; progenitor cell.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein Receptors, Type I / genetics
  • Bone Morphogenetic Protein Receptors, Type I / metabolism
  • Bone Morphogenetic Proteins / metabolism
  • Cell Differentiation / physiology*
  • Dermis / cytology
  • GATA3 Transcription Factor / metabolism
  • Hair Follicle / cytology*
  • Hair Follicle / metabolism
  • Hedgehog Proteins / deficiency
  • Hedgehog Proteins / genetics
  • Keratin-6 / metabolism
  • Keratins / genetics
  • Keratins / metabolism
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction

Substances

  • Bone Morphogenetic Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Hedgehog Proteins
  • Keratin-6
  • Krt75 protein, mouse
  • Shh protein, mouse
  • keratin 79, mouse
  • Keratins
  • Bmpr1a protein, mouse
  • Bone Morphogenetic Protein Receptors, Type I