title: WNT-SHH Antagonism Specifies and Expands Stem Cells prior to Niche Formation.
abstract: Adult stem cell (SC) maintenance and differentiation are known to depend on signals received from the niche. Here, however, we demonstrate a mechanism for SC specification and regulation that is niche independent. Using immunofluorescence, live imaging, genetics, cell-cycle analyses, in utero lentiviral transduction, and lineage-tracing, we show that in developing hair buds, SCs are born from asymmetric divisions that differentially display WNT and SHH signaling. Displaced WNT(lo) suprabasal daughters become SCs that respond to paracrine SHH and symmetrically expand. By contrast, basal daughters remain WNT(hi). They express but do not respond to SHH and hence maintain slow-cycling, asymmetric divisions. Over time, they become short-lived progenitors, generating differentiating daughters rather than SCs. Thus, in contrast to an established niche that harbors a fixed SC pool whose expelled progeny differentiate, asymmetric divisions first specify and displace early SCs into an environment conducive to expansion and later restrict their numbers by switching asymmetric fates.
authors.affiliation: Robin Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Ouspenskaia
authors.affiliation: Robin Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Matos
authors.affiliation: Robin Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Mertz
authors.affiliation: Robin Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Vincent F
authors.initials: VF
authors.lastname: Fiore
authors.affiliation: Robin Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA. Electronic address: fuchslb@rockefeller.edu.
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D002455:Cell Division; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D051379:Mice / Q000196:embryology*; D008856:Microscopy, Fluorescence; D055758:SOX9 Transcription Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D053823:Hedgehog Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse