The signaling protein Wnt4 enhances thymopoiesis and expands multipotent hematopoietic progenitors through beta-catenin-independent signaling.
Immunity
; 29(1): 57-67, 2008 Jul 18.
Article
em En
| MEDLINE
| ID: mdl-18617424
ABSTRACT
Despite studies based on deletion or activation of intracellular components of the canonical Wingless related (Wnt) pathway, the role of Wnts in hematolymphopoiesis remains controversial. Using gain-of-function and loss-of-function models, we found that Wnt4 differentially affected diverse subsets of hematopoietic stem and progenitor cells. Bone-marrow and thymic Lin(-)Sca1(+)Kit(hi) cells (LSKs) were the key targets of Wnt4. In adult mice, Wnt4-induced expansion of Flt3(+) bone-marrow LSKs (lymphoid-primed multipotent progenitors) led to a sizeable accumulation of the most immature thymocyte subsets (upstream of beta-selection) and a major increase in thymopoiesis. Conversely, Wnt4(-/-) neonates showed low frequencies of bone-marrow LSKs and thymic hypocellularity. We provide compelling evidence that Wnt4 activates noncanonical (beta-catenin-independent) signaling and that its effects on hematopoietic cells are mainly non-cell-autonomous. Our work shows that Wnt4 overexpression has a unique ability to expand Flt3(+) LSKs in adults and demonstrates that noncanonical Wnt signaling regulates thymopoiesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timo
/
Células-Tronco Hematopoéticas
/
Transdução de Sinais
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Células-Tronco Multipotentes
/
Proteínas Wnt
/
Beta Catenina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Immunity
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Canadá