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Notch signalling via RBP‐J promotes myeloid differentiation
Author(s) -
Schroeder Timm,
Just Ursula
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.11.2558
Subject(s) - biology , myelopoiesis , transactivation , microbiology and biotechnology , notch signaling pathway , myeloid , haematopoiesis , cellular differentiation , notch proteins , context (archaeology) , progenitor cell , signal transduction , immunology , stem cell , transcription factor , genetics , paleontology , gene
The expression of Notch receptors on hematopoietic cells and of cognate ligands on bone marrow stromal cells suggests a possible role for Notch signalling in the regulation of hematopoiesis. In order to assess the involvement of Notch1 signalling in myelopoiesis, 32D myeloid progenitor cell lines were engineered to permit the conditional induction of the constitutively active intracellular domain of murine Notch1 (mN1 IC ) by the 4‐hydroxytamoxifen‐inducible system. The induction of mN1 IC resulted in accelerated and increased granulocytic differentiation. These effects were observed under growth conditions that support differentiation and, to a lesser degree, under conditions that normally promote self‐renewal. Transient transfection of mN1 IC deletion mutants showed that the differentiation promoting activity correlated with RBP‐J transactivation. Furthermore, expression of a transcriptionally active derivative of RBP‐J (RBP‐J–VP16) increased myeloid differentiation. To test further the role of Notch signalling in a physiological context, 32D cells expressing mNotch1 were cultured on fibroblast layers that either expressed or did not express the Notch ligand Jagged1. Similar to the induction of mN1 IC , Jagged1 accelerated granulocytic differentiation of 32D cells. Taken together, our data suggest that activation of mNotch1 promotes myeloid differentiation via RBP‐J transactivation.