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骨髓间充质基质细胞克隆群体中的干细胞相关基因表达。

Stem cell-related gene expression in clonal populations of mesenchymal stromal cells from bone marrow.

机构信息

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.

出版信息

Tissue Eng Part A. 2010 Feb;16(2):749-58. doi: 10.1089/ten.TEA.2009.0307.

Abstract

Decline in the frequency of potent mesenchymal stem cells (MSCs) has been implicated in ageing and degenerative diseases. Increasing the circulating stem cell population can lead to renewed recruitment of these potent cells at sites of damage. Therefore, identifying the ideal cells for ex vivo expansion will form a major pursuit of clinical applications. This study is a follow-up of previous work that demonstrated the occurrence of fast-growing multipotential cells from the bone marrow samples. To investigate the molecular processes involved in the existence of such varying populations, gene expression studies were performed between fast- and slow-growing clonal populations to identify potential genetic markers associated with stemness using the quantitative real-time polymerase chain reaction comprising a series of 84 genes related to stem cell pathways. A group of 10 genes were commonly overrepresented in the fast-growing stem cell clones. These included genes that encode proteins involved in the maintenance of embryonic and neural stem cell renewal (sex-determining region Y-box 2, notch homolog 1, and delta-like 3), proteins associated with chondrogenesis (aggrecan and collagen 2 A1), growth factors (bone morphogenetic protein 2 and insulin-like growth factor 1), an endodermal organogenesis protein (forkhead box a2), and proteins associated with cell-fate specification (fibroblast growth factor 2 and cell division cycle 2). Expression of diverse differentiation genes in MSC clones suggests that these commonly expressed genes may confer the maintenance of multipotentiality and self-renewal of MSCs.

摘要

随着年龄的增长和退行性疾病的发生,间充质干细胞(MSCs)的频率逐渐下降。增加循环中的干细胞数量可以导致这些多能细胞在损伤部位重新募集。因此,鉴定用于体外扩增的理想细胞将成为临床应用的主要目标。本研究是对先前工作的后续研究,该研究表明骨髓样本中存在快速生长的多潜能细胞。为了研究参与这种不同群体存在的分子过程,在快速和缓慢生长的克隆群体之间进行了基因表达研究,以使用包含与干细胞途径相关的 84 个基因的定量实时聚合酶链反应来鉴定与干性相关的潜在遗传标记。一组 10 个基因在快速生长的干细胞克隆中普遍过表达。这些基因包括编码参与维持胚胎和神经干细胞更新的蛋白(性别决定区 Y 框 2、同源盒 1 和 delta 样 3)、与软骨生成相关的蛋白(聚集蛋白聚糖和胶原 2A1)、生长因子(骨形态发生蛋白 2 和胰岛素样生长因子 1)、内胚层器官发生蛋白(叉头框 A2)和与细胞命运特化相关的蛋白(成纤维细胞生长因子 2 和细胞分裂周期蛋白 2)。MSC 克隆中多种分化基因的表达表明,这些共同表达的基因可能赋予 MSC 的多能性和自我更新能力。

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