Investigating effect of telomerase on differentiation of human embryonic stem cells and expansion of the progenitors

研究端粒酶对人胚胎干细胞分化和祖细胞扩增的影响

• 批准号: G0802537/1
• 负责人: Wei Cui
• 金额: $ 42.61万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0802537%2F1
• 关键词: Investigating; effect; telomerase; differentiation; human

Ageing is a natural process that all living organisms have to bear. When humans get older, the incidence for certain conditions and diseases becomes much higher, such as infection, cancer, Alzheimer s and Parkinson s diseases. This is mainly due to special cells that normally protect human, by replacing non-functional cells or responding to stress conditions (e.g. infection), cease to function properly. These cells called adult stem cells. The secret behind this lies in part with a structure that caps both ends of every chromosome in our cells. These structures are telomeres , consisting primarily of an array of thousands of DNA TTAGGG repeats. The main function of telomeres is to keep the chromosomes in good order so that all the genetic information can be faithfully passed from mother cells to daughter cells. The telomere DNA can only be synthesized by a special enzyme complex, called telomerase . In normal human development, telomerase is restricted to be active in germ cells and early embryos (and cells derived from early embryos e.g. embryonic stem cells) but absent in most of the cells in the body. In the adult stem cells, telomerase is active but at very low levels. Hence, in the majority of cells, including stem cells, telomeres are shortened each time that cells divide and eventually, telomeres get too short to protect chromosome ends and cells will stop dividing or they even die. However, in cancer cells, telomerase expression is higher thus enabling the cancer cells to divide indefinitely. Therefore, telomerase is like a double-edged sword: its absence may account for adult stem cell ageing but on the other hand, its expression may lead to cancer.It remains unclear what function telomerase plays in human development and cancer. If telomerase is highly active in adult stem cells, does it prevent stem cell ageing or does it produce cancer? Also, do stem cells with active telomerase can develop into functional cell types (e.g. heart cells, liver cells and brain cells)? In this project, we will investigate these issues using cell and molecular biology techniques in a specific cell model system. Answers to these questions will provide important information about telomerase function in development, ageing and cancer. The information will also help scientists and medical doctors to use stem cells for the treatment of age-related diseases.

衰老是所有生物体都必须承受的自然过程。当人类变老时，某些病症和疾病的发病率会变得更高，例如感染、癌症、阿尔茨海默病和帕金森病。这主要是由于通常保护人类的特殊细胞通过替换无功能的细胞或对应激条件（例如感染）做出反应而停止正常运作。这些细胞称为成体干细胞。这背后的秘密部分在于我们细胞中每条染色体两端的结构。这些结构是端粒，主要由数千个 DNA TTAGGG 重复序列组成。端粒的主要功能是保持染色体良好的秩序，以便所有遗传信息能够忠实地从母细胞传递到子细胞。端粒 DNA 只能由一种特殊的酶复合物（称为端粒酶）合成。在正常人类发育中，端粒酶仅限于在生殖细胞和早期胚胎（以及源自早期胚胎的细胞，例如胚胎干细胞）中活跃，但在体内的大多数细胞中不存在。在成体干细胞中，端粒酶是活跃的，但水平非常低。因此，在包括干细胞在内的大多数细胞中，每次细胞分裂时端粒都会缩短，最终端粒变得太短而无法保护染色体末端，细胞将停止分裂甚至死亡。然而，在癌细胞中，端粒酶表达较高，从而使癌细胞能够无限分裂。因此，端粒酶就像一把双刃剑：它的缺失可能导致成体干细胞衰老，但另一方面，它的表达可能导致癌症。目前尚不清楚端粒酶在人类发育和癌症中发挥什么作用。如果端粒酶在成体干细胞中高度活跃，它会阻止干细胞衰老还是会产生癌症吗？另外，具有活性端粒酶的干细胞可以发育成功能性细胞类型（例如心脏细胞、肝细胞和脑细胞）吗？在这个项目中，我们将在特定的细胞模型系统中使用细胞和分子生物学技术来研究这些问题。这些问题的答案将提供有关端粒酶在发育、衰老和癌症中的功能的重要信息。这些信息还将帮助科学家和医生利用干细胞治疗与年龄相关的疾病。