Fate Before Function: Specification of the Hair Follicle Niche Occurs Prior to its Formation and Is Progenitor Dependent

Abstract

Cell fate transitions are essential for specialization of stem cells and their niches, but the precise timing and sequence of molecular events during embryonic development are largely unknown. Here, we show that dermal condensates (DC), signaling niches for epithelial progenitors in hair placodes, are specified before niche formation and function. With 3D/4D microscopy we identify unclustered DC precursors. With population-based and single-cell transcriptomics we define a molecular time-lapse of dynamic niche signatures and 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 consolidate DC niche formation. Finally, ablation of epidermal Wnt signaling and placode-derived FGF20 demonstrates their requirement for DC-precursor specification. These findings uncover a progenitor-dependent niche precursor fate and the transitory molecular events controlling niche formation and function.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/414839_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (78K):\norg.highwire.dtl.DTLVardef@13fa73aorg.highwire.dtl.DTLVardef@1fbd280org.highwire.dtl.DTLVardef@1b8f66borg.highwire.dtl.DTLVardef@3a1ef9_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIPrecursors of the hair follicle niche are specified before niche cluster formation\nC_LIO_LIBulk/single cell RNA-seq defines early niche fate at molecular transitional state\nC_LIO_LISuccessive waves of transcription factor/signaling genes mark niche fate acquisition\nC_LIO_LINiche fate acquisition is not \"pre-programmed\" and requires FGF20 from progenitors\nC_LI