title: Transit-amplifying cells orchestrate stem cell activity and tissue regeneration.
abstract: Transit-amplifying cells (TACs) are an early intermediate in tissue regeneration. Here, using hair follicles (HFs) as a paradigm, we show that emerging TACs constitute a signaling center that orchestrates tissue growth. Whereas primed stem cells (SCs) generate TACs, quiescent SCs only proliferate after TACs form and begin expressing Sonic Hedgehog (SHH). TAC generation is independent of autocrine SHH, but the TAC pool wanes if they can't produce SHH. We trace this paradox to two direct actions of SHH: promoting quiescent-SC proliferation and regulating dermal factors that stoke TAC expansion. Ingrained within quiescent SCs' special sensitivity to SHH signaling is their high expression of GAS1. Without sufficient input from quiescent SCs, replenishment of primed SCs for the next hair cycle is compromised, delaying regeneration and eventually leading to regeneration failure. Our findings unveil TACs as transient but indispensable integrators of SC niche components and reveal an intriguing interdependency of primed and quiescent SC populations on tissue regeneration.
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Ya-Chieh
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Lishi
authors.initials: L
authors.lastname: Li
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: fuchslb@rockefeller.edu.
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006197:Hair / Q000166:cytology* / Q000502:physiology*; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D051379:Mice; D012038:Regeneration; D015398:Signal Transduction; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse