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PMID:15845452
| Citation |
Rupec, RA, Jundt, F, Rebholz, B, Eckelt, B, Weindl, G, Herzinger, T, Flaig, MJ, Moosmann, S, Plewig, G, Dörken, B, Förster, I, Huss, R and Pfeffer, K (2005) Stroma-mediated dysregulation of myelopoiesis in mice lacking I kappa B alpha. Immunity 22:479-91 |
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| Abstract |
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. |
| Links |
PubMed Online version:10.1016/j.immuni.2005.02.009 |
| Keywords |
Alleles; Animals; Calcium-Binding Proteins; Down-Regulation; Gene Deletion; Gene Expression Regulation; Hematopoietic System/physiology; Humans; I-kappa B Proteins/genetics; I-kappa B Proteins/physiology; Intercellular Signaling Peptides and Proteins; Liver/cytology; Liver/embryology; Liver/growth & development; Membrane Proteins; Mice; Myelopoiesis/genetics; Myeloproliferative Disorders/genetics; Proteins/metabolism; Signal Transduction; Stromal Cells/cytology; Stromal Cells/physiology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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