WNT-SHH Antagonism Specifies and Expands Stem Cells prior to Niche Formation.
Cell
; 164(1-2): 156-169, 2016 Jan 14.
Article
em En
| MEDLINE
| ID: mdl-26771489
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Folículo Piloso
/
Proteínas Hedgehog
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Via de Sinalização Wnt
/
Camundongos
Limite:
Animals
Idioma:
En
Revista:
Cell
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos