Inhibition of granulocytic differentiation by mNotch1
Inhibition of granulocytic differentiation by mNotch1
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DOI：
10.1073/pnas.93.23.13014
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发表时间：
1996-11-12
影响因子：
11.1
通讯作者：
Martin, DIK
中科院分区：
文献类型：
--
作者：
Milner, LA;Bigas, A;Martin, DIK
有效的造血需要多能干细胞致力于不同的分化途径、不同谱系细胞的增殖和成熟，以及保存多能祖细胞以提供成熟血细胞的持续更新。虽然正和负细胞因子在调节造血细胞增殖和成熟中的重要性已得到充分证明，但参与多能祖细胞谱系定型和自我更新的因素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相互作用已被证明会影响多能祖细胞对细胞命运的决定。我们之前描述了人类 Notch1 同源物 TAN-1 在未成熟造血前体细胞中的表达。我们非；证明小鼠Notch1的激活的细胞内结构域在32D骨髓祖细胞中的组成型表达抑制粒细胞分化并允许未分化细胞的扩增，这一发现与Notch在其他系统中的已知功能一致。
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 non; 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.