Dissecting the molecular basis of mesoderm formation
Recent technical advancements in human embryonic stem cells have revolutionized their potential applications in regenerative medicine. However, a remaining big hurdle in this process is the need for efficient, effective, and stable generation of specific cell types from such stem cells for therapeutic usage. The proposed research focuses on studying a special cell type in our embryo, called mesoderm. Mesoderm gives rise to a number of tissues and structures including bone, cartilage, muscle, connective tissue, the urinary system, the reproductive system, heart, and the dermis of the skin. For example, heart failure often requires heart transplant, which is limited by the lack of matched donors and severe side effects due to immunosuppressant therapy. Heart regeneration from mesoderm tissues derived from human embryonic stem cells or induced pluripotent stem cells would greatly improve heart failure treatment. To regenerate mesoderm-derived tissues for tissue repair, it is critical to understand what are the genes and signaling pathways that control human mesoderm formation. To date, there is little information on how human mesoderm is formed due to the inability to study this event in embryo. This proposal takes advantage of the use of human embryonic stem cells to develop mesoderm in culture to study mesoderm development. We will first test a group of genes for their roles in mesoderm formation. Then we will develop a novel reporter system to label and purify emerging human mesoderm cells and identify and study novel genes involved in human mesoderm development. Completion of this project would provide valuable insight into the key factors in mesoderm differentiation, which is essential for efficient generation of mesoderm-derived tissues for therapeutic usage.
Stem cell therapy has the potential to revolutionize the treatment of many common diseases that afflict residents of the State of California. For example, thousands of Californians suffer from heart failure and need heart transplant for survival. However, these life-saving measures are limited by a lack of eligible donors and the necessity of finding correctly matched donors. Recent technical advancements in human embryonic stem cell and induced pluripotent stem cell production have revolutionized their potential applications in regenerative medicine and have provided enormous hope for these patients. Producing therapeutically useful differentiated cells from pluripotent stem cells is a critical step in clinical application. Our proposal will provide a better understanding of the mechanisms involved in producing mesoderm, which then gives rise to many critical tissues in our body, including heart, bone, cartilage, and muscle. One long-term benefit of the proposed research is to allow effective generations of various mesoderm-derive cell types and tissues for tissue repair. In addition, the involved work will include the training and education of some of California's bright young minds to become leaders of stem cell research and maintain California as a world leader in regeneration medicine.