| First Author | Louis I | Year | 2008 |
| Journal | Immunity | Volume | 29 |
| Issue | 1 | Pages | 57-67 |
| PubMed ID | 18617424 | Mgi Jnum | J:137842 |
| Mgi Id | MGI:3803049 | Doi | 10.1016/j.immuni.2008.04.023 |
| Citation | Louis I, et al. (2008) The signaling protein Wnt4 enhances thymopoiesis and expands multipotent hematopoietic progenitors through beta-catenin-independent signaling. Immunity 29(1):57-67 |
| abstractText | 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. |
