Density of the Notch ligand Delta1 determines generation of B and T cell precursors from hematopoietic stem cells.
Density of the Notch ligand Delta1 determines generation of B and T cell precursors from hematopoietic stem cells.
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Notch配体delta1的密度决定了造血干细胞的B和T细胞前体的产生。
DOI：
10.1084/jem.20042450
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发表时间：
2005-05-02
影响因子：
15.3
通讯作者：
Bernstein, ID
中科院分区：
文献类型：
--
作者：
Dallas, MH;Varnum- Finney, B;Delaney, C;Kato, K;Bernstein, ID
Noch信号通过造血祖细胞调节多个细胞的命运。为了解决不同数量的Notch配体是否会影响谱系选择，我们培养了小鼠骨髓LIN−Sca-1+c-Kit+细胞，并增加了固定化Delta1ext-Ig G的密度，该固定化Delta1Ext-Ig G由Delta1胞外域与人Ig G1Fc域融合组成。我们发现相对低密度的Delta1ext-Ig G可促进Sca-1+c-Kit+细胞、Thy1+CD25+早期T细胞前体细胞和B220+CD43CD43−/lo细胞的产生，当与OP9基质细胞共培养时，这些细胞分化为CD19+早期B细胞前体细胞。较高浓度的Delta1ext-Ig G可促进Sca-1+c-Kit+前体细胞的产生，促进Thy1+CD2 5+细胞的发育，但对B2 2 0+CD4 3−/lo细胞的发育有抑制作用。对进一步分离的前体群体的分析表明，T和B细胞前体的增强生成是由于对多潜能前体的影响，而不是对淋巴系承诺的前体的影响。这些结果证明了Delta1在多个成熟阶段对造血祖细胞命运决定的密度依赖效应，并证实了先前未知的Delta1促进早期B和T前体细胞发育的能力。
Notch signaling regulates multiple cell fate decisions by hematopoietic precursors. To address whether different amounts of Notch ligand influence lineage choices, we cultured murine bone marrow lin−Sca-1+c-kit+ cells with increasing densities of immobilized Delta1ext-IgG consisting of the extracellular domain of Delta1 fused to the Fc domain of human IgG1. We found that relatively lower densities of Delta1ext-IgG enhanced the generation of Sca-1+c-kit+ cells, Thy1+CD25+ early T cell precursors, and B220+CD43−/lo cells that, when cocultured with OP9 stroma cells, differentiated into CD19+ early B cell precursors. Higher densities of Delta1ext-IgG also enhanced the generation of Sca-1+c-kit+ precursor cells and promoted the development of Thy1+CD25+ cells, but inhibited the development of B220+CD43−/lo cells. Analyses of further isolated precursor populations suggested that the enhanced generation of T and B cell precursors resulted from the effects on multipotent rather than lymphoid-committed precursors. The results demonstrate the density-dependent effects of Delta1 on fate decisions of hematopoietic precursors at multiple maturational stages and substantiate the previously unrecognized ability of Delta1 to enhance the development of both early B and T precursor cells.
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影响因子：
20.3
作者：
Dorsch, M;Zheng, G;Villeval, JL
通讯作者：
Villeval, JL
影响因子：
20.3
作者：
Jones, P;May, G;Enver, T
通讯作者：
Enver, T
影响因子：
20.3
作者：
Varnum-Finney, B;Purton, LE;Bernstein, ID
通讯作者：
Bernstein, ID
影响因子：
20.3
作者：
Varnum-Finney, B;Brashem-Stein, C;Bernstein, ID
通讯作者：
Bernstein, ID
影响因子：
4.4
作者：
Felli, MP;Maroder, M;Screpanti, I
通讯作者：
Screpanti, I