dlk inhibits stem cell factor-induced colony formation of murine hematopoietic progenitors: Hes-1-independent effect.
Delta-like (dlk) is a family of transmembrane proteins containing epidermal growth factor-like repeat motifs homologous to the notch/delta/serrate family. Recent studies suggest that dlk is a negative regulator of adipocyte differentiation, a promoting factor of cobblestone area colony formation, and a molecule which influences stromal cell-pre-B cell interactions and augments cellularity of developing thymocytes. However, the role of dlk in regulating the growth and differentiation of hematopoietic progenitors remains unclear. In the present study, we examined the effect of dlk on the proliferation of murine hematopoietic progenitors by hematopoietic growth factors. Soluble dlk-IgG Fc chimeric protein completely inhibited the colony formation of lineage-marker negative (Lin-) bone marrow cells by GM-CSF, G-CSF, or macrophage-CSF (M-CSF) in the presence of stem cell factor (SCF). However, dlk failed to inhibit the colony formation of Lin- bone marrow cells by CSF, as described above, or M-CSF plus interleukin 3. Furthermore, dlk failed to inhibit the colony formation of Hes-1-null fetal liver cells by M-CSF in the presence of SCF. These findings suggest that dlk is an important regulator of hematopoietic progenitor proliferation. Depending on the presence of SCF, dlk may act as a growth inhibitor, although dlk signaling does not mediate Hes-1 transcription factor.
Ohno
N
N
Pharmaceutical Research Laboratories, Toray Industries, Inc., Tebiro, Kamakura, Japan.
Izawa
A
A
Hattori
M
M
Kageyama
R
R
Sudo
T
T
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000166:cytology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology* / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D018398:Homeodomain Proteins; D007377:Interleukin-3; D047908:Intracellular Signaling Peptides and Proteins; D016173:Macrophage Colony-Stimulating Factor; D008565:Membrane Proteins; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C064045:delta protein; C078493:HES1 protein, human