A soluble form of human Delta-like-1 inhibits differentiation of hematopoietic progenitor cells

作     者：Han, W Ye, Q Moore, MAS 

作者机构：Mem Sloan Kettering Canc Ctr Lab Dev Hematopoiesis New York NY 10021 USA 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第95卷第5期

页      面：1616-1625页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NCI NIH HHS [CA-08748] Funding Source: Medline NHLBI NIH HHS [1-F32-HL10152-01] Funding Source: Medline 

主　　题：氨基酸序列 抗原 分化/分析 细胞凋亡/药物作用 细胞凋亡/生理学 骨髓细胞/细胞学 骨髓细胞/药物作用 骨髓细胞/代谢 细胞分化/药物作用 细胞分化/生理学 细胞系 集落形成单位测定 DNA 互补/遗传学 流式细胞术 基因表达调控/药物作用 血细胞生成/药物作用 血细胞生成/生理学 造血细胞生长因子/药理学 造血干细胞/细胞学 造血干细胞/药物作用 膜蛋白质类/遗传学 膜蛋白质类/代谢 膜蛋白质类/生理学 分子序列数据 RNA 信使/生物合成 受体 Notch 重组融合蛋白质类/生理学 序列比对 序列同源性 氨基酸 种特异性 间质细胞/代谢 动物 人类 小鼠 

摘      要：Two Notch ligand families, Delta and Serrate/Jagged, have been identified in vertebrates. Members of the Jagged family have been shown to affect in vitro hematopoiesis. To determine whether members of the Delta family might play a similar role in hematopoiesis, we examined the expression of mouse Delta like-1 (mDII1), mDII1 protein was detected in whole marrow and in a marrow stromal cell line MS-5. At the RNA level, both mDII1 and Notch1 were seen in marrow precursor, differentiated hematopoietic, marrow stromal, and MS-5 cells. We isolated a cDNA encoding the human homologue of mDII1, designated human Delta-like-1 (hDII1). A soluble form of hDII1, hDII1(NDSL), containing the DSL domain and the N-terminal sequences, was expressed and purified from bacteria as a glutathione S-transferase (GST) fusion protein. We observed that hDII1(NDSL) delayed the acquisition of differentiation markers by murine hematopoietic progenitor cells (Lin(-)) cultured in vitro with cytokines. In addition, it promoted greater expansion (more than 3 times) of the primitive hematopoietic precursor cell population, measured in high-proliferative potential colony assay and day 12 colony-forming unit spleen (CFU-S) assay, than GST controls. We also observed that the percentage of apoptotic cells decreased and that the number of cells in the S-phase of the cell cycle increased in the cultures of Lin- cells with hDII1NDSL The effects of hDII1NDSL were blocked by antibody against the mouse counterpart of hDII1(NDSL), mDII1(NDSL). These observations demonstrate that hDII1 plays a role in mediating cell fate decisions during hematopoiesis. (C) 2000 by The American Society of Hematology.