Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Stroma-mediated dysregulation of myelopoiesis in mice lacking IkappaBalpha

Official URL:https://doi.org/10.1016/j.immuni.2005.02.009
PubMed:View item in PubMed
Creators Name:Rupec, R.A. and Jundt, F. and Rebholz, B. and Eckelt, B. and Weindl, G.N. and Herzinger, T. and Flaig, M.J. and Moosmann, S. and Plewig, G. and Doerken, B. and Foerster, I. and Huss, R. and Pfeffer, K.
Journal Title:Immunity
Journal Abbreviation:Immunity
Volume:22
Page Range:479-491
Date:1 January 2005
Keywords:Alleles, Calcium-Binding Proteins, Down-Regulation, Gene Deletion, Gene Expression Regulation, Hematopoietic System, I-kappa B Proteins, Intercellular Signaling Peptides and Proteins, Liver, Membrane Proteins, Myelopoiesis, Myeloproliferative Disorders, Proteins, Signal Transduction, Stromal Cells, Animals, Mice
Abstract:Hematopoiesis occurs in the liver and the bone marrow (BM) during murine development. Newborn mice with a ubiquitous deletion of IκBα 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 IκBα-deficient hepatocytes. The result is a permanent activation of Notch1 in neutrophils. In contrast, in mice with a conditional deletion of IκBα only in the myeloid lineage (ikbaflox/flox × LysM-Cre) and in fetal liver cell chimeras (ikbaFLΔ/FLΔ), a cell-autonomous induction of the myeloproliferative disease was not observed. Coculture of IκBα-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 IκBα.
ISSN:1074-7613
Item Type:Article

Repository Staff Only: item control page

Open Access
MDC Library