| First Author | Rupec RA | Year | 2005 |
| Journal | Immunity | Volume | 22 |
| Issue | 4 | Pages | 479-91 |
| PubMed ID | 15845452 | Mgi Jnum | J:97945 |
| Mgi Id | MGI:3576806 | Doi | 10.1016/j.immuni.2005.02.009 |
| Citation | Rupec RA, et al. (2005) Stroma-mediated dysregulation of myelopoiesis in mice lacking I kappa B alpha. Immunity 22(4):479-91 |
| abstractText | Hematopoiesis occurs in the liver and the bone marrow (BM) during murine development. Newborn mice with a ubiquitous deletion of I kappa B alpha develop a severe hematological disorder characterized by an increase of granulocyte/erythroid/monocyte/macrophage colony-forming units (CFU-GEMM) and hypergranulopoiesis. Here, we report that this particular myeloproliferative disturbance is mediated by continuously deregulated perinatal expression of Jagged1 in I kappa B alpha-deficient hepatocytes. The result is a permanent activation of Notch1 in neutrophils. In contrast, in mice with a conditional deletion of I kappa B alpha only in the myeloid lineage (ikba(flox/flox) x LysM-Cre) and in fetal liver cell chimeras (ikba(FL delta/FL delta)), a cell-autonomous induction of the myeloproliferative disease was not observed. Coculture of I kappa B alpha-deficient hepatocytes with wild-type (wt) BM cells induced a Jagged1-dependent increase in CFUs. In summary, we show that cell-fate decisions leading to a premalignant hematopoietic disorder can be initiated by nonhematopoietic cells with inactive I kappa B alpha. |
