Oct4 over-expression promotes cardiomyocyte proliferation- Lessons learning from iPSing cells

• Main Authors: Chia-Yi Hsieh, 謝家漪
• Other Authors: Hsiao-Sheng Liu
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/75553599878274963368

碩士 === 國立成功大學 === 微生物暨免疫學研究所 === 97 === Congestive heart failure is the primary cause of death in the world. The limitation of heart regeneration has been ascribed to the low degree of cell mitosis in cardiomyocytes. Cardiac injuries, such as myocardial infarction, cause cardiomyocyte death and scar tissue displacement, leading to irreversible functional impairment. How to prevent apoptosis or promote proliferation of cardiomyocytes is thus important. Non-mammalian vertebrate heart has regenerative capacity, and may occur through cardiac progenitor cell differentiation. In 2006, Yamanaka’s group reported the use of four factors (Oct4, Sox2, Klf4, and c-Myc), which are crucial to pluripotent maintenance on embryonic stem cells, to reprogram mouse fibroblasts into induced pluripotent stem (iPS) cells. Base on Yamanaka’s idea, we try to use iPS-inducing factors and early cardiac markers to promote the reprogramming and/or proliferation of fully differentiated cardiomyocytes. First, we established the lentivirus gene delivery system to enhance cardiomyocyte transfection efficiency. Using propidium iodide staining, we found that only Oct4 overexpression promoted cardiomyocyte proliferation. Additionally, we examined cell cycle related gene expression by RT-PCR and immunoblotting, and demonstrated that cyclin A2, cyclin B1, Aurora B, and phospho-histone H3 (H3P) were induced upon Oct4 expression. Furthermore, we observed Oct4-transduced cardiomyocytes undergoing karyokinesis and cytokinesis by staining cell mitosis markers such as H3P, AuroraB and Survivin. Oct4 was observed to co-exist with Ki-67 in the nucleus. Therefore, it is likely that Oct4 promotes cardiomyocyte proliferation by regulating cell cycle related molecules. In accordance with our immunoblotting data, this regulation probably was through Akt independent pathway. In summary, we found that the iPS factor Oct4 has the potential to promote cardiomyocyte proliferation. These preliminary data provide an attractive method to treat heart diseases.