Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation

Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation
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DOI:
10.1182/blood-2004-08-3207
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发表时间:
2005-03-15
期刊:
影响因子:
20.3
通讯作者:
Radtke, F
Radtke, F
中科院分区:
医学1区
文献类型:
--
作者:
Mancini, SJC;Mantei, N;Radtke, F

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Jagged 1介导的Notch信号转导被认为与造血干细胞(HSC)的自我更新密切相关。出乎意料的是,我们在这里报告,诱导Cre-loxP介导的锯齿状蛋白1基因在骨髓祖细胞和/或骨髓(BM)基质细胞的失活不损害HSC的自我更新或分化在所有的血液谱系。在BM隔室中同时失活Jagged 1和Notch 1的小鼠在基于5 FU的体内攻击后正常存活。此外,Notch 1缺陷型HSC能够在灭活的竞争条件下重建小鼠。与早期的报道相反,这些数据排除了Jagged 1介导的Notch信号在造血过程中的重要作用。BM基质中的锯齿状1,甚至低于美国血液学学会2005年(c)。
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 competitive conditions. In contrast to earlier reports, these data exclude an essential role for Jagged1-mediated Notch signaling during hematopoiesis. Jagged1 in the BM stroma even under (c) 2005 by The American Society of Hematology.