Milner L A, Bigas A, Kopan R, Brashem-Stein C, Bernstein I D, Martin D I
Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle 98104, USA.
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13014-9. doi: 10.1073/pnas.93.23.13014.
Effective hematopoiesis requires the commitment of pluripotent and multipotent stem cells to distinct differentiation pathways, proliferation and maturation of cells in the various lineages, and preservation of pluripotent progenitors to provide continuous renewal of mature blood cells. While the importance of positive and negative cytokines in regulating proliferation and maturation of hematopoietic cells has been well documented, the factors and molecular processes involved in lineage commitment and self-renewal of multipotent progenitors have not yet been defined. In other developmental systems, cellular interactions mediated by members of the Notch gene family have been shown to influence cell fate determination by multipotent progenitors. We previously described the expression of the human Notch1 homolog, TAN-1, in immature hematopoietic precursors. We now demonstrate that constitutive expression of the activated intracellular domain of mouse Notch1 in 32D myeloid progenitors inhibits granulocytic differentiation and permits expansion of undifferentiated cells, findings consistent with the known function of Notch in other systems.
有效的造血作用需要多能和多潜能干细胞定向分化为不同的细胞系，各细胞系中的细胞进行增殖和成熟，并保留多能祖细胞以持续更新成熟血细胞。虽然正负细胞因子在调节造血细胞增殖和成熟中的重要性已有充分记录，但多能祖细胞的谱系定向和自我更新所涉及的因子和分子过程尚未明确。在其他发育系统中，Notch基因家族成员介导的细胞间相互作用已显示出会影响多能祖细胞的细胞命运决定。我们之前描述过人Notch1同源物TAN-1在未成熟造血前体细胞中的表达。我们现在证明，在32D髓系祖细胞中组成型表达小鼠Notch1的活化细胞内结构域可抑制粒细胞分化并允许未分化细胞扩增，这一发现与Notch在其他系统中的已知功能一致。
