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Updated: Jun 2, 2026

08:01
Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
骨髄性白血病におけるノッチ経路のための新しい腫瘍抑制機能
Apostolos Klinakis1, Camille Lobry, Omar Abdel-Wahab
1Biomedical Research Foundation, Academy of Athens, Athens, Greece.
Nature
|May 13, 2011
まとめ
ノッチ・シグナリングは,通常,細胞の分化を調節する. この研究では,Notchシグナル伝達における不活性化変異が,血液形成性幹細胞の分化を阻害することによって慢性骨髄性単細胞性白血病 (CMML) を引き起こしていることが判明しました.
科学分野:
- 血液学 ヘマトロジ
- 分子生物学は分子生物学である.
- がん生物学 がん生物学
背景:
- γ-分泌酵素 (γSE) 複合体によって調節されるノッチシグナル伝達は,細胞の分化に極めて重要です.
- Notchシグナリングは,固体腫瘍において二重の役割を果たしますが,T細胞急性リンパ性白血病など,主として造血系において腫瘍性です.
- 慢性骨髄性白血病 (CMML) での役割は不明である.
研究 の 目的:
- 慢性骨髄性白血病 (CMML) のノッチ信号の役割を調査する.
- CMML患者におけるノッチ経路に影響を与える新しい突然変異を特定する.
- 造血幹細胞 (HSC) のノッチ経路不活性化による機能的影響を解明する.
主な方法:
- CMML患者のサンプルにおける体的変異分析.
- ネズミの造血幹細胞 (HSC) のノッチ信号の無効化.
- 血液形成原始体集団とマウスの疾患誘導の分析.
- 制御された遺伝子発現シグネチャーを特定するためのトランスクリプトーム分析.
主要な成果:
- ノッチ経路における新しい体内無活性化変異は,CMML患者で特定されました.
- マウスのHSCにおけるNotchシグナリングの無活性化により,粒細胞/単細胞原始体 (GMP) の蓄積とCMMLのような疾患が発生した.
- ノッチ・シグナリングは,ミエロモノサイトに特有の遺伝子シグネチャを調節することが判明しました.
- ノッチの標的であるHes1は,ノッチの調節作用を媒介して,遺伝子転写を直接抑制する.
結論:
- ノッチ・シグナリングは,初期のHSCの差別化において,新しい抑制的な役割を果たします.
- Notch信号の無効化は,CMMLの病原化に寄与する.
- Notch経路は,同じ組織内で,文脈に依存する腫瘍抑制機能と腫瘍促進機能を示す.
関連する概念動画
Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
