Stroma-mediated dysregulation of myelopoiesis in mice lacking IkappaBalpha

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Item Type:	Article
Title:	Stroma-mediated dysregulation of myelopoiesis in mice lacking IkappaBalpha
Creators Name:	Rupec, R.A., Jundt, F., Rebholz, B., Eckelt, B., Weindl, G.N., Herzinger, T., Flaig, M.J., Moosmann, S., Plewig, G., Doerken, B., Foerster, I., Huss, R. and Pfeffer, K.
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.
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
Source:	Immunity
ISSN:	1074-7613
Volume:	22
Page Range:	479-491
Date:	1 January 2005
Official Publication:	https://doi.org/10.1016/j.immuni.2005.02.009
PubMed:	View item in PubMed

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