| First Author | Janzen V | Year | 2008 |
| Journal | Cell Stem Cell | Volume | 2 |
| Issue | 6 | Pages | 584-94 |
| PubMed ID | 18522851 | Mgi Jnum | J:149797 |
| Mgi Id | MGI:3849145 | Doi | 10.1016/j.stem.2008.03.012 |
| Citation | Janzen V, et al. (2008) Hematopoietic stem cell responsiveness to exogenous signals is limited by caspase-3. Cell Stem Cell 2(6):584-94 |
| abstractText | Limited responsiveness to inflammatory cytokines is a feature of adult hematopoietic stem cells and contributes to the relative quiescence and durability of the stem cell population in vivo. Here we report that the executioner Caspase, Caspase-3, unexpectedly participates in that process. Mice deficient in Caspase-3 had increased numbers of immunophenotypic long-term repopulating stem cells in association with multiple functional changes, most prominently cell cycling. Though these changes were cell autonomous, they reflected altered activation by exogenous signals. Caspase-3(-/-) cells exhibited cell type-specific changes in phosphorylated members of the Ras-Raf-MEK-ERK pathway in response to specific cytokines, while notably, members of other pathways, such as pSTAT3, pSTAT5, pAKT, pp38 MAPK, pSmad2, and pSmad3, were unaffected. Caspase-3 contributes to stem cell quiescence, dampening specific signaling events and thereby cell responsiveness to microenvironmental stimuli. |
