Establishing cell lines that can reproducibly generate cell types of interest is critical to translational use of stem cells, both for cell replacement therapy and for generating human disease models. Generation of pluripotent stem cells produces induced pluripotent (iPSC) and embryonic stem cell (ESC) lines that differ in their capacity to produce specific differentiated cell types. We have established a set of "fully pluripotent" mouse iPSCs that can reproducibly generate all cell types in an adult animal and have identified a novel set of potential biomarkers that distinguish these cells from less potent cell lines. We hypothesize that these biomarkers will identify human iPSCs and ESCs that can generate the widest variety of clinically-relevant cell types. We base this hypothesis on our preliminary studies and evidence for similarities in core regulators of pluripotency and self-renewal between mouse and human cells. We will exploit our unique set of cell lines and apply state-of-the-art proteomic and genetic analyses to discover new biomarkers of fully pluripotent human stem cells. Results of these experiments will remove a bottleneck in stem cell research that currently adds uncertainty to the validity of in vitro disease models and increases the cost of establishing clinically suitable cell lines and differentiation protocols. Identifying novel biomarkers of pluripotency should impact stem cell research across disciplines and establish needed molecular standards for cell banking and maintenance.
Statement of Benefit to California:
Pluripotent stem cells derived from embryos (ESCs) or from differentiated cells ( iPSCS) offer a unique source of human specific cell types for drug screening and cell replacement therapy. The most useful cell lines are those which are capable of generating all the different cell types useful for therapy, such as neurons for treatments of Alzheimer's, Parkinson's disease and spinal cord injury, pancreatic beta cells for treatment of diabetes or heart cells for cardiovascular defects. Some ESCs and iPSCs are better than others at generating particular cell types. Current tests to identify such cells are costly, difficult, time-consuming and not optimally effective. This proposal aims to identify simple and cost effective methods to identify the most useful ESCs and iPSCs by discovering new markers found on the cells that generate the most different cell types. These studies will reduce the costs of establishing and maintaining pluripotent cell lines in many laboratories and should help to standardize stem cell- based clinical trials. This proposal will benefit California by reducing research costs, accelerating the time to therapies and helping to establish the most useful banks of stem cells for future research and clinical applications.