The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1

The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1
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DOI:
10.1016/s1074-7613(00)80457-4
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发表时间:
1998-01-01
期刊:
影响因子:
32.4
通讯作者:
Torok-Storb, B
Torok-Storb, B
中科院分区:
医学1区
文献类型:
--
作者:
Li, LH;Milner, LA;Torok-Storb, B

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从正常人骨髓中分离出编码大鼠Jagged 1的人同源物的cDNA克隆。人基质细胞系的分析表明,该基因,命名为hJagged 1,由骨髓基质细胞表达,代表细胞系HS-27 a,支持造血祖细胞的长期维持。G-CSF诱导的表达Notch 1的32 D细胞的分化通过与HS-27 a共培养而被抑制。对应于hJagged 1的Delta/Serrate/LAG-2结构域的肽和来自表达hJagged 1的细胞外部分的可溶形式的COS细胞的上清液能够模拟这种作用。这些观察结果表明,hJagged 1可能作为Notch 1的配体发挥作用,并在造血过程中介导细胞命运的决定中发挥作用。
A cDNA clone encoding the human homolog of rat Jagged1 was isolated from normal human marrow. Analyses of human stromal cell lines indicate that this gene, designated hJagged1, is expressed by marrow stromal cells typified by the cell line HS-27a, which supports the long-term maintenance of hematopoietic progenitor cells. G-CSF-induced differentiation of 32D cells expressing Notch1 was inhibited by coculturing with HS-27a. A peptide corresponding to the Delta/Serrate/LAG-2 domain of hJagged1 and supernatants from COS cells expressing a soluble form of the extracellular portion of hJagged1 were able to mimic this effect. These observations suggest that hJagged1 may function as a ligand for Notch1 and play a role in mediating cell fate decisions during hematopoiesis.