Investigation of the mechanism that initiates the molecular heterogeneity in human embryonic stem cells
Human embryonic stem cells (hESCs) can give rise to virtually all types of specialized adult cells in human body. Thus they are thought to be the potential source of the cell-transplantation therapy for the treatment of diseases such as Parkinson's disease, myocardial infarction, and diabetes mellitus. While hESC research has made a considerable progress in developing methods to generate specialized cell types including neurons, cardiomyocytes, and insulin-secreting cells, studies to identify the key mechanisms that allow hESCs to maintain such an enormous differentiation capacity (pluripotency) have just begun. Because obtaining the pure undifferentiated cell population establishes the basis of hESCs-based therapeutic approach, these studies are essential to find the way to grow hESCs without losing their pluripotency. Moreover, as the recent findings have shown that hESCs grown under the current culture condition are not homogenous, but rather mosaic of different populations which may contain cells that have less differentiation capacity, it is critical to understand how this heterogeneity has occurred during the propagation process of hESCs.
The goal of the proposed study is to determine the core mechanism that generates mixed populations in hESCs which prevents them from keeping their differentiation capacity throughout the propagation process. Our preliminary data have indicated that a specific signaling pathway (like a hormone that mediates various biological information) may be responsible for making inhomogeneous populations in hESCs. Based on this finding, we will focus on investigating the role of the signaling pathway in hESCs through a series of molecular experiments, and developing the novel technology which enables us to grow hESCs as a pure population of undifferentiated cells that would further standardize the hESCs-based therapeutic strategy.
Our research will focus on identifying the mechanism that regulates the multiple differentiation capacity (pluripotency) in hESCs. With the knowledge obtained through the project, we will concentrate on developing a novel technology that will allow us to culture uniformly pluripotent hESCs which is not possible under the current culture protocols.
The establishment of such a new method would impact virtually all hESCs-based application programs as it involves a common basic process to expand hESCs before turning into any type of adult cells for the therapeutic purposes.
It is therefore predictable that the new methodology will be promptly translated as an intellectual property to be commercialized, and would substantially activate the biotechnology field in the State of California.
More importantly, the new methodology will be provided to the Institutes in California at the highest priority where the method will accelerate the process to apply the hESCs-based transplantation approach for the clinical settings that would further contribute to the enhancement of the medical environment for California citizens.