Dermal Condensate Niche Fate Specification Occurs Prior to Formation and Is Placode Progenitor Dependent

Dev Cell. 2019 Jan 7;48(1):32-48.e5. doi: 10.1016/j.devcel.2018.11.034. Epub 2018 Dec 27.

Abstract

Cell fate transitions are essential for specification of stem cells and their niches, but the precise timing and sequence of molecular events during embryonic development are largely unknown. Here, we identify, with 3D and 4D microscopy, unclustered precursors of dermal condensates (DC), signaling niches for epithelial progenitors in hair placodes. With population-based and single-cell transcriptomics, we define a molecular time-lapse from pre-DC fate specification through DC niche formation and establish the developmental trajectory as the DC lineage emerges from fibroblasts. Co-expression of downregulated fibroblast and upregulated DC genes in niche precursors reveals a transitory molecular state following a proliferation shutdown. Waves of transcription factor and signaling molecule expression then coincide with DC formation. Finally, ablation of epidermal Wnt signaling and placode-derived FGF20 demonstrates their requirement for pre-DC specification. These findings uncover a progenitor-dependent niche precursor fate and the transitory molecular events controlling niche formation and function.

Keywords: cell fate specification; dermal condensate precursors; dermal papilla; hair follicle formation; hair follicle morphogenesis; placode progenitors; single cell; stem cell niche.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Dermis / metabolism*
  • Fibroblasts / cytology
  • Gene Expression Regulation, Developmental / physiology*
  • Hair Follicle / embryology
  • Hair Follicle / metabolism*
  • Signal Transduction / genetics
  • Skin / metabolism
  • Stem Cells / cytology