机械敏感基因增强剂增强细胞对矩阵刚性的反应
Brian D Cosgrove1,2, Lexi R Bounds1,2, Carson Key Taylor1,2
1Department of Biomedical Engineering, Duke University, Durham, NC, USA.
概括
科学家发现了机械增强剂, 编辑这些增强可以重新编程细胞反应, 提供治疗机械驱动疾病的潜力.
科学领域:
- 分子生物学
- 细胞生物学
- 表观遗传学
背景情况:
- 细胞微环境显著影响基因表达和细胞表型的表观遗传调节.
- 机械线索影响表观遗传状态以控制转录的精确机制尚未完全理解.
研究的目的:
- 在微环境中响应机械线索的基因组元素.
- 研究这些元素在调节细胞功能和与疾病相关的基因激活中的作用.
主要方法:
- 全基因组表观基因组分析
- 表观基因组编辑技术
- 表型分析
- 单细胞RNA测序CRISPR查
主要成果:
- 鉴定了一种新型基因组增强剂,称为"机械增强剂",由基质刚性激活.
- 机械增强剂调节关键细胞功能,包括细胞亡,粘附,增殖和迁移.
- 机械增强剂的表观遗传编辑改变了肺纤维细胞对机械刺激的细胞反应,并调节了与疾病相关的基因表达.
结论:
- 机械增强剂代表了机械微环境和转录的表观遗传调节之间的直接联系.
- 通过表观基因编辑准机械增强剂为机械驱动疾病 (如纤维化) 提供了有前途的治疗策略.
相关概念视频
Cell-matrix's Response to Mechanical Forces
3.4K
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
3.4K
Tension Response at Adherens Junctions
3.5K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
3.5K
Overview of Cell-Matrix Interactions
8.9K
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
8.9K
The Extracellular Matrix
88.2K
Overview
88.2K
The Extracellular Matrix
11.9K
Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
11.9K
Extracellular Matrix
5.2K
Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
5.2K


