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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2340-2342.
Prepublished online as a Blood First Edition Paper on November 18, 2004; DOI 10.1182/blood-2004-08-3207.
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Submitted August 19, 2004
Accepted November 12, 2004
Jagged1 dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation
Stephane J Mancini, Ned Mantei, Alexis Dumortier, Ueli Suter, H R MacDonald, and Freddy Radtke*
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland
Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, Zurich, Switzerland
* Corresponding author; email: freddy.radtke{at}isrec.unil.ch.
Jagged1 mediated Notch signaling has been suggested to be critically involved in hematopoietic stem cell (HSC) self-renewal. Unexpectedly, we report here that inducible Cre-loxP mediated inactivation of the Jagged1 gene in bone marrow progenitors and/or BM stromal cells does not impair HSC self-renewal or differentiation in all blood lineages. Mice with simultaneous inactivation of Jagged1 and Notch1 in the BM compartment survived normally following a 5FU-based in vivo challenge. In addition, Notch1 deficient HSCs were able to reconstitute mice with inactivated Jagged1 in the BM stroma even under competitive conditions. In contrast to earlier reports, these data exclude an essential role for Jagged1 mediated Notch signaling during hematopoiesis.
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