罕见的肺神经内分泌细胞是通过Rb,p53和Notch调节的干细胞
Youcef Ouadah1, Enrique R Rojas2, Daniel P Riordan3
1Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Cancer Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|October 5, 2019
概括
罕见的肺神经内分泌细胞作为干细胞, 在受伤后再生肺组织. 它们的失调与小细胞肺癌的发展有关.
科学领域:
- 肺部生物学
- 干细胞研究
- 癌症学
背景情况:
- 肺神经内分泌 (NE) 细胞是支气管上皮中的神经传感细胞.
- 这些细胞繁殖和分化,帮助肺部在受伤后恢复.
研究的目的:
- 确定在肺修复过程中作为干细胞的特定NE细胞.
- 了解调节NE干细胞行为的机制及其与小细胞肺癌 (SCLC) 的联系.
主要方法:
- 研究肺损伤后的NE细胞增殖,迁移和分化.
- 分析了瘤抑制剂 (Rb,p53) 和诺奇信号在NE干细胞调节中的作用.
主要成果:
- 鉴定出具有自我更新和迁移能力的罕见NE细胞 (每组2-4个).
- 观察到NE干细胞失去身份,放大和分化以修复肺上皮.
- 证明Rb和p53抑制NE干细胞的自我更新,而Notch信号则启动了脱编程和放大.
结论:
- 肺部NE干细胞对于肺上皮的修复至关重要.
- 由SCLC瘤抑制剂影响的NE干细胞更新和脱编程的失调被认为是SCLC瘤发生的机制.
相关概念视频
Negative Regulator Molecules
38.2K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.2K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.4K
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...
2.4K
Notch Signaling Pathway
6.3K
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...
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...
6.3K
Stem Cell Niche
6.1K
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
6.1K
Abnormal Proliferation
5.0K
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...
5.0K
The Retinoblastoma Gene
4.6K
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.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.6K


