GSE122026
Dermal Condensate Niche Fate Specification Occurs Prior to Formation and Is Placode Progenitor Dependent
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/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. Overall design: Dorsal skins were dissected from E15.0 embryos, dissociated into single cells, and FACS sorted. Single-cell transcriptomics was performed on live cells using an automated version of CEL-seq2 on live, FACS sorted cells. The StemID algorithm was used to identify clusters of cells corresponding to stages of DC development, starting from fibroblasts. Bulk RNA-sequencing of sorted populations from E15.0 backskin; raw data files contain all transcriptome information for pre-DC, DC1, DC2, fibroblasts, Schwann cells, and negative population, processed data file includes transcriptome information for pre-DC, DC1, DC2, fibroblasts, Schwann cells and negative population used in this study. Single Cell RNA-sequencing of E15.0 mouse backskin; raw data files contain all single cell transcriptome information, processed data file includes mesenchymal transcriptome information used in this study.