中枢神经系统前代细胞衰老的原因
Michael Segel1,2, Björn Neumann1,2, Myfanwy F E Hill1,2
1Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Nature
|August 16, 2019
概括
随着年龄的增长,组织的硬程度会增加,从而损害中枢神经系统 (CNS) 的干细胞功能. 恢复年轻的机械信号使这些细胞复苏,突显了PIEZO1在与年龄相关的衰退和潜在的再生疗法的作用.
科学领域:
- 神经科学
- 干细胞生物学
- 老年学
背景情况:
- 由于干细胞和祖细胞功能障碍,衰老导致组织再生减少.
- 中枢神经系统的原生细胞 (OPC) 随着年龄的增长呈现再生能力的下降.
- 包括机械线索在内的干细胞位是与年龄相关的功能衰退的一个低估因素.
研究的目的:
- 研究中枢神经系统微环境与年龄相关的变化对OPC功能的影响.
- 确定的机械特性是否足以导致与年龄相关的OPC功能障碍.
- 确定OPC中介于机械信号的分子机制,并探索治疗干预措施.
主要方法:
- 使用生物和合成支架来模仿不同的组织硬性.
- 在不同机械性能的支架上培养过的OPC.
- 研究了PIEZO1离子通道在OPC中介导机械信号的作用.
- 在体内和体外破坏了机械信号通道.
主要成果:
- OPC微环境随着年龄的增长而变硬,导致功能衰退.
- 在年轻的模仿大脑支架上培养老年OPC导致了分子和功能复苏.
- 破坏机械信号增强了OPC的扩散和分化.
- PIEZO1被确定为机械信号的关键媒介,其抑制可以在衰老的中枢神经系统中保持OPC活性.
结论:
- 组织硬是中枢神经系统OPC衰老的关键调节者.
- 调节机械可以使老旧的OPC恢复功能.
- 抑制PIEZO1是一种潜在的治疗策略,可以抵消与年龄相关的干细胞功能障碍并促进中枢神经系统的再生.
相关概念视频
02:02Ecological Niches
26.1K
All organisms have a position within an ecosystem. The complete set of living and nonliving factors—including food resources, climate, and terrain—that define the position of a given organism are collectively referred to as the organism’s ecological niche.
26.1K
01:25What is a Nervous System?
104.3K
Overview
104.3K
01:26Stem Cell Niche
6.3K
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...
6.3K
01:14The Parasympathetic Nervous System
115.0K
Overview
115.0K
01:25The Sympathetic Nervous System
103.1K
Overview
103.1K
01:06Multipotency and Niche of Bulge Stem Cell
4.2K
A hair follicle or HF is a small part of the skin that produces the hair shaft. Paul Gerson Unna was the first to observe a bulge in the human hair follicle's outer root sheath (ORS). The bulge is present between the sebaceous gland and the arrector pili muscle and is the niche for hair follicle stem cells (HFSCs). The bulge is also a niche for melanocyte stem cells, and their loss results in graying of hair. The HFSCs express Sox9 and Lhx2, which help them maintain stemness and prevent...
4.2K