Ohno N, Izawa A, Hattori M, Kageyama R, Sudo T
Pharmaceutical Research Laboratories, Toray Industries, Inc., Tebiro, Kamakura, Japan.
Stem Cells. 2001;19(1):71-9. doi: 10.1634/stemcells.19-1-71.
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.
Delta样蛋白（dlk）是一类跨膜蛋白家族，含有与Notch/Delta/锯齿蛋白家族同源的表皮生长因子样重复基序。最近的研究表明，dlk是脂肪细胞分化的负调节因子，是鹅卵石区域集落形成的促进因子，并且是一种影响基质细胞与前B细胞相互作用并增加发育中胸腺细胞细胞数量的分子。然而，dlk在调节造血祖细胞生长和分化中的作用仍不清楚。在本研究中，我们研究了dlk对造血生长因子作用下小鼠造血祖细胞增殖的影响。在干细胞因子（SCF）存在的情况下，可溶性dlk-IgG Fc嵌合蛋白完全抑制了GM-CSF、G-CSF或巨噬细胞集落刺激因子（M-CSF）诱导的谱系标记阴性（Lin-）骨髓细胞的集落形成。然而，如上所述，dlk未能抑制CSF或M-CSF加白细胞介素3诱导的Lin-骨髓细胞的集落形成。此外，在SCF存在的情况下，dlk未能抑制M-CSF诱导的Hes-1基因敲除胎肝细胞的集落形成。这些发现表明，dlk是造血祖细胞增殖的重要调节因子。根据SCF的存在情况，dlk可能作为生长抑制剂起作用，尽管dlk信号传导不介导Hes-1转录因子。
