Stromal expression of Jagged 1 promotes colony formation by fetal hematopoietic progenitor cells

Stromal expression of Jagged 1 promotes colony formation by fetal hematopoietic progenitor cells
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DOI:
10.1182/blood.v92.5.1505.417k42_1505_1511
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发表时间:
1998-09-01
期刊:
影响因子:
20.3
通讯作者:
Enver, T
Enver, T
中科院分区:
医学1区
文献类型:
--
作者:
Jones, P;May, G;Enver, T

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被引文献

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Notch信号系统调节许多组织的增殖和分化。Noch是一种跨膜受体,由相邻细胞上表达的配体激活。造血干细胞和早期祖细胞表达Notch,使与祖细胞形成细胞接触的基质细胞成为造血微环境中的候选配体呈递细胞。因此,我们检查了原代基质鳗鱼培养物中Notch配体的表达。利用逆转录-聚合酶链式反应、原位杂交、免疫组织化学和Western blotting,我们证实了Jagge1在原代基质培养中的表达。为了研究Jagge1的间质表达是否对造血祖细胞有功能影响,我们在Jagge1(-)基质细胞系S17和表达Jagge1的S17细胞上培养了11日龄小鼠中肾区的CD34(+),c-kit(+)造血祖细胞。在随后的甲基纤维素培养中,Jagge1的存在使集落数增加了四倍。在相同的培养条件下,D11胎肝来源的CD34(+)、c-kit(+)造血祖细胞的集落数有较大增加。这些结果在体外获得了表格Jagge1,作为体内基质微环境背景下干细胞命运的候选调节因子。(C)1998年由美国血液病学会主办。
The Notch signaling system regulates proliferation and differentiation in many tissues. Notch is a transmembrane receptor activated by ligands expressed on adjacent cells. Hematopoietic stem cells and early progenitors express Notch, making the stromal cells which form cell-cell contacts with progenitor cells candidate ligand-presenting cells in the hematopoietic microenvironment. Therefore, we examined primary stromal eel cultures for expression of Notch ligands. Using reverse transcription-polymerase chain reaction, in situ hybridization, immunohistochemistry, and Western blotting, we demonstrate expression of Jagged 1 in primary stromal cultures. To investigate if the stromal expression of Jagged 1 has functional effects on hematopoietic progenitors, we cultured CD34(+), c-kit(+) hematopoietic progenitor cells derived from the aorto gonadal mesonephros region of day 11 mouse embryos on the Jagged 1(-) stromal cell line S17 and on S17 cells engineered to express Jagged 1. The presence of Jagged 1 increased the number of colonies formed in subsequent methylcellulose culture fourfold. Larger increases in colony numbers were observed under the same culture conditions with CD34(+), c-kit(+) hematopoietic progenitor cells derived from d11 fetal liver. These results obtained in vitro table Jagged 1 as a candidate regulator of stem cell fate in the context of stromal microenvironments in vivo. (C) 1998 by The American Society of Hematology.