在患有全身性硬化症的患者中改变了角质化,细胞外矩阵生成,血管新生和树突干细胞增殖的途径
Amelia Spinella1, Domenico Lo Tartaro2, Lara Gibellini2
1Scleroderma Unit and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, University Hospital of Modena Policlinico of Modena, Modena, Italy.
Journal of scleroderma and related disorders
|June 8, 2023
概括
系统性硬化症涉及与皮肤角质化和干细胞增殖减少相关的独特基因表达模式. 这项研究确定了系统性硬化症患者潜在生物标志物和治疗的关键途径.
科学领域:
- 免疫学 免疫学 免疫学
- 皮肤病学 皮肤病学
- 基因组学就是基因组学.
背景情况:
- 系统性硬化症 (SSc) 是一种复杂的自身免疫性疾病,其特征是内皮功能障碍,免疫系统异常以及影响皮肤和内脏器官的渐进性纤维化.
- 驱动SSc血管病变,纤维细胞激活和细胞外基质沉积的精确病原遗传机制仍然不完全理解.
- 现有研究强调了细胞和细胞外因素的复杂相互作用,但主要驱动因素尚不清楚.
研究的目的:
- 通过转录组分析识别与SSc病变发生,内皮功能障碍和纤维化相关的功能途径和潜在生物标志物.
- 为了比较SSc患者和健康对照者之间的基因表达特征,以发现疾病特异性的分子特征.
- 为开发新型诊断标记物和SSc.治疗策略奠定基础.
主要方法:
- 对三名SSc患者和三名健康对照的组织活检进行了RNA测序.
- 转录组分析涉及生成测序库和对差异表达基因进行基因组丰富分析.
- 对完整的RNA测序表达矩阵进行了途径分析,以确定丰富的生物过程.
主要成果:
- 健康对照组表现出与干细胞增殖和免疫细胞代谢相关的基因特征.
- 在SSc组织中,基因签名与角质化,角化和细胞周期调节相关 (RB1,TP53信号传递).
- 在SSc中差异性基因表达与角质化,细胞外矩阵生成和血管生成和干细胞增殖的负调节有关.
结论:
- RNA测序和途径分析揭示了SSc患者的独特基因表达模式,其特征是角质化和受损的树皮干细胞增殖.
- 这些发现表明化途径的潜在作用,并突出了SSc.中血管生成和干细胞增殖的负调节.
- 虽然需要在更大的队列中进一步验证,但这些结果为开发SSc生物标志物和未来治疗干预提供了有希望的框架.
相关概念视频
01:12Renewal of Skin Epidermal Stem Cells
2.6K
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
2.6K
01:19Clinical Applications of Epidermal Stem Cells
2.7K
Epidermal stem cells (EpiSCs) are mainly located at the basal layer of the epidermis. These cells repair minor injuries of the skin and replace dead skin cells. However, EpiSCs’ cannot heal severe wounds such as major burns or those from diabetes or hereditary disorders. In such cases, culturing the epidermal stem cells from the patient is possible and has yielded successful treatment options, such as laboratory-grown skin grafts. These grafts are synthesized using a patient’s own...
2.7K
01:26Stem Cell Niche
5.2K
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...
5.2K
01:26Extracellular Matrix
3.0K
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...
3.0K
01:22iPS Cell Differentiation
2.8K
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
2.8K
02:17The Tumor Microenvironment
6.7K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.7K