Mancini Stéphane J C, Mantei Ned, Dumortier Alexis, Suter Ueli, MacDonald H Robson, Radtke Freddy
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland.
Blood. 2005 Mar 15;105(6):2340-2. doi: 10.1182/blood-2004-08-3207. Epub 2004 Nov 18.
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 bone marrow (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.
已有研究表明，锯齿状蛋白1（Jagged1）介导的Notch信号通路在造血干细胞（HSC）自我更新中起关键作用。出乎意料的是，我们在此报告，通过诱导型Cre-loxP介导的骨髓祖细胞和/或骨髓（BM）基质细胞中Jagged1基因的失活，并不会损害HSC的自我更新或所有血细胞谱系的分化。在基于5-氟尿嘧啶（5FU）的体内挑战后，BM区室中Jagged1和Notch1同时失活的小鼠正常存活。此外，即使在竞争条件下，Notch1缺陷的HSC也能够在BM基质中重建Jagged1失活的小鼠。与早期报告相反，这些数据排除了Jagged1介导的Notch信号通路在造血过程中的重要作用。
