基于染色体和新陈代谢重塑的机械记忆促进了介质干细胞的增殖和平滑肌肉分化
Jing Na1, Qiusheng Shi1, Zhijie Yang1
1Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
概括
介酶干细胞 (MSCs) 记住机械线索,影响它们的治疗潜力. 这种机械记忆涉及染色素,新陈代谢和细胞相互作用,为干细胞治疗提供了新的途径.
科学领域:
- 生物医学工程 生物医学工程
- 细胞生物学 细胞生物学
- 再生医学是一种再生医学.
背景情况:
- 干细胞的治疗作用是由它们微环境中的机械线索调节的.
- 染色体组织和能量代谢是机械影响下干细胞命运的关键调节者.
- 干细胞机械记忆背后的精确机制在很大程度上是未知的.
研究的目的:
- 研究机械振幅,频率,持续时间和拉伸周期如何影响中细胞干细胞 (MSCs) 的机械记忆.
- 阐明MSC机械记忆的分子和细胞基础.
- 探索机械记忆在干细胞应用中的潜在治疗影响.
主要方法:
- 使用不同参数 (振幅,频率,持续时间,拉伸周期) 机械刺激MSC.
- 细胞对齐,细胞骨成分 (F-actin,paxillin) 和核变形的分析.
- 转录变化和代谢活动的评估,包括线粒体动态和ATP生产.
- 对表观遗传修饰的研究,特别是素H3素27三甲基化.
- 评价细胞与细胞相互作用及其在机械记忆传输中的作用.
主要成果:
- 机械振幅被确定为影响细胞对齐持续性的主要因素.
- 虽然细胞对齐显示出一些持久性,但F-actin,paxillin和核变形更容易重塑.
- 拉伸诱导了转录记忆,在随后的机械重新加载时导致增强基因表达.
- 细胞代谢表现出机械记忆,其特点是持续的线粒体融合和增加的ATP生产.
- 机械记忆的染色质凝聚,通过素H3氨酸27三甲基化介导,显著提高了光滑肌肉差异化效率.
- 机械记忆可以通过直接的细胞与细胞接触进行转移,伸展的细胞会影响相邻静态细胞的代谢状态.
结论:
- 介质细胞干细胞具有强大的机械记忆,受各种物理参数的影响.
- 这种记忆涉及表观遗传修饰,转录调节和代谢适应.
- 机械记忆可以在细胞之间传输,这表明细胞的反应是协调的.
- 了解和利用MSC中的机械记忆对于增强基于干细胞的疗法具有重大前景.
相关概念视频
01:32Chromatin Modification in iPS Cells
1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K
01:14Maintenance of the ES Cell State
2.2K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.2K
01:26Stem Cell Niche
5.1K
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...
5.1K
01:29Somatic to iPS Cell Reprogramming
2.2K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.2K
03:17Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K
01:19Mesenchymal Stem Cells
4.7K
Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
4.7K