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

衰老是所有生物体都必须承受的自然过程。当人类变老时，某些疾病的发病率会变得更高，如感染，癌症，阿尔茨海默氏症和帕金森氏症。这主要是由于通常保护人类的特殊细胞，通过替换非功能性细胞或应对压力条件（例如感染），停止正常工作。这些细胞被称为成体干细胞。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的良好秩序，使所有的遗传信息可以忠实地从母细胞传递到子细胞。端粒DNA只能由一种称为端粒酶的特殊酶复合物合成。在正常的人类发育中，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）中有活性，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，但水平很低。因此，在大多数细胞中，包括干细胞，端粒在每次细胞分裂时都会缩短，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，端粒酶表达更高，从而使癌细胞能够无限分裂。因此，端粒酶是一把双刃剑：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，端粒酶在人类发育和癌症中的作用尚不清楚。如果端粒酶在成体干细胞中高度活跃，那么它会阻止干细胞老化还是会产生癌症？此外，具有活性端粒酶的干细胞是否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）？在这个项目中，我们将在一个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使用干细胞治疗与年龄有关的疾病。

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.