RT Journal Article
SR Electronic
T1 Fate Before Function: Specification of the Hair Follicle Niche Occurs Prior to its Formation and Is Progenitor Dependent
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 414839
DO 10.1101/414839
A1 Ka-Wai Mok
A1 Nivedita Saxena
A1 Nicholas Heitman
A1 Laura Grisanti
A1 Devika Srivastava
A1 Mauro Muraro
A1 Tina Jacob
A1 Rachel Sennett
A1 Zichen Wang
A1 Yutao Su
A1 Lu M. Yang
A1 Avi Ma’ayan
A1 David M. Ornitz
A1 Maria Kasper
A1 Michael Rendl
YR 2018
UL http://biorxiv.org/content/early/2018/09/12/414839.abstract
AB 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.HIGHLIGHTSPrecursors of the hair follicle niche are specified before niche cluster formationBulk/single cell RNA-seq defines early niche fate at molecular transitional stateSuccessive waves of transcription factor/signaling genes mark niche fate acquisitionNiche fate acquisition is not “pre-programmed” and requires FGF20 from progenitors