| First Author | Ming M | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 27 | Pages | 22683-90 |
| PubMed ID | 22589536 | Mgi Jnum | J:330489 |
| Mgi Id | MGI:6854965 | Doi | 10.1074/jbc.M112.342089 |
| Citation | Ming M, et al. (2012) Activation of Wnt/beta-catenin protein signaling induces mitochondria-mediated apoptosis in hematopoietic progenitor cells. J Biol Chem 287(27):22683-90 |
| abstractText | The canonical Wnt/beta-catenin signaling is activated during development, tumorigenesis, and in adult homeostasis, yet its role in maintenance of hematopoietic stem/progenitor cells is not firmly established. Here, we demonstrate that conditional expression of an active form of beta-catenin in vivo induces a marked increase in the frequency of apoptosis in hematopoietic stem/progenitor cells (HSCs/HPCs). Activation of Wnt/beta-catenin signaling in HPCs in vitro elevates the activity of caspases 3 and 9 and leads to a loss of mitochondrial membrane potential (DeltaPsi(m)), indicating that it induces the intrinsic mitochondrial apoptotic pathway. In vivo, expression of activated beta-catenin in HPCs is associated with down-regulation of Bcl2 and expression of Casp3. Bone marrow transplantation assays reveal that enhanced cell survival by a Bcl2 transgene re-establishes the reconstitution capacity of HSCs/HPCs that express activated beta-catenin. In addition, a Bcl2 transgene prevents exhaustion of these HSCs/HPCs in vivo. Our data suggest that activation of the Wnt/beta-catenin pathway contributes to the defective function of HPCs in part by deregulating their survival. |
