A soluble form of human Delta-like-1 inhibits differentiation of hematopoietic progenitor cells Journal Article
| Authors: | Han, W.; Ye, Q.; Moore, M. A. S. |
| Article Title: | A soluble form of human Delta-like-1 inhibits differentiation of hematopoietic progenitor cells |
| Abstract: | 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 hDII1(NDSL). The effects of hDII1(NDSL) 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. |
| Keywords: | immunohistochemistry; protein expression; gene sequence; flow cytometry; animals; mice; bone marrow cells; cell cycle s phase; apoptosis; cell line; protein; membrane proteins; cell fate; cell differentiation; gene expression regulation; amino acid sequence; molecular sequence data; sequence homology, amino acid; species specificity; hybrid protein; amino terminal sequence; recombinant fusion proteins; rna, messenger; sequence alignment; receptors, notch; ligand; glutathione transferase; hematopoietic stem cells; hematopoiesis; hematopoietic stem cell; colony-forming units assay; stromal cells; antigens, differentiation; dna, complementary; humans; priority journal; article; colony forming unit s; hematopoietic cell growth factors |
| Journal Title: | Blood |
| Volume: | 95 |
| Issue: | 5 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2000-03-01 |
| Start Page: | 1616 |
| End Page: | 1625 |
| Language: | English |
| PUBMED: | 10688816 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood.V95.5.1616.005k31_1616_1625 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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