Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability
Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability
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DOI：
10.1182/blood-2002-06-1862
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发表时间：
2003-03-01
期刊：
影响因子：
20.3
通讯作者：
Bernstein, ID
中科院分区：
文献类型：
--
作者：
Varnum-Finney, B;Brashem-Stein, C;Bernstein, ID
我们研究了工程化Notch配体和造血生长因子诱导的联合信号传导是否影响造血干细胞分化。我们发现，小鼠骨髓前体细胞与 Delta1(ext-IgG)（一种由与人免疫球蛋白 G1 (IgG1) Fc 部分融合的 Delta1 细胞外结构域组成的 Notch 配体）和生长因子、干细胞因子 (SCF)、白细胞介素 6 (IL-6)、IL-11 和 Flt3-1 一起孵育，可抑制骨髓分化，并促进能够短期淋巴和分化的前体细胞数量增加几个对数。骨髓再生。添加IL7促进早期T细胞发育，而添加粒细胞-巨噬细胞集落刺激因子(GM-CSF)导致终末骨髓分化。这些结果支持Notch和细胞因子诱导的信号通路的组合效应在调节造血细胞命运中的作用，并表明Notch配体在增加临床干细胞移植的造血前体数量方面的有用性。
We investigated whether combined signaling induced by engineered, Notch ligands and hematopoietic growth factors influences hernatopoietic stem-cell differentiation. We show that incubation of murine marrow precursors with Delta1(ext-IgG), a Notch ligand consisting of the Delta1 extracellular domain fused to the Fc portion of human immunoglobulin G1 (IgG1), and growth factors stem cell factor (SCF), interleukin 6 (IL-6), IL-11, and Flt3-1 inhibited myeloid differentiation and promoted a several-log increase in the number of precursors capable of short-term lymphoid and myeloid repopulation. Addition of IL7 promoted early T-cell development, whereas addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) led to terminal myeloid differentiation. These results support a role for combinatorial effects by Notch and cytokine-induced signaling pathways in regulating hernatopoietic cell fate and suggest the usefulness of Notch ligand in increasing hematopoietic precursor numbers for clinical stem-cell transplantation.