PROJECT SUMMARY Research and experimental use of pluripotent stem cells has expanded rapidly, and these cells now provide important research models of human disease and personalized regenerative medicine. However, the majority of research to date that has utilized stem cells has employed genetically-limited murine cells or clonal human cell lines with little attention paid to the impact of cellular genetic diversity on the phenotypic and functional outcomes and its relevance to human diversity. Importantly, recent data from murine and human studies of pluripotent stem cells indicate that genetic variability is the most significant driver of molecular and cellular differences in phenotype, including the ease of establishment of pluripotent cell lines, the rate of spontaneous differentiation, reprogramming differentiated cells to a pluripotent state, and the future use of stem cells as personalized therapeutics. Thus, there is now an unmet need, not rigorously addressed at current conferences, to understand the consequences of genetic variation on stem cell biology and their impact on development. To fill this gap, we propose the unique and timely conference “Diversity in a Dish: Pluripotent Stem Cells in Genetic Analysis and Disease Modeling” to facilitate interdisciplinary interactions and collaborations between experts in mouse and human genetics, cell biology, and pluripotency, and to engage diverse learners who are the next generation of stem cell researchers. We propose an annual, intensive 3-day conference beginning in 2023 at The Jackson Laboratory in Bar Harbor, ME. We will bring together 50 scientists, spanning career stages, from the fields of genetics, cell biology, and pluripotency, as well as provide a virtual attendance option for those that cannot or choose not to attend in person. For Aim 1, we will convene an interdisciplinary symposium organized around cutting-edge research seminars, workshops that focus on technical skill acquisition, and rigor and reproducibility as applied to stem cell research and genomic analyses. In Aim 2, we will promote interactive and inclusive activities, to promote networking, mentorship, learner involvement, collaborative research, and career development. These activities include trainee presentations and short talks, and evening discussions focused on research projects, rigor and ethics, and grantsmanship. These objectives are facilitated by the residential nature of the JAX Highseas Conference Center. In Aim 3, we will promote diversity in both the recruitment of participants and in the tools being generated to study models of human disease. Diverse attendees will be actively recruited, scholarships will be provided to enable in-person attendance, and an inclusive virtual option will enable participation by those that are unable to travel. Diversity will also be emphasized in the context of best practices for research, including the need for studies of genetically diverse panels of stem cells, and fair acquisition, representation, and distribution of cell lines from wider representation of backgrounds to ensure the benefits discovered from these biomedical resources are shared equitably.

PROJECT NARRATIVE / RELEVANCE TO PUBLIC HEALTH Genetic diversity is central to the biology of human health and disease but is often overlooked when developing tractable disease models. Thus, to accelerate our understanding of the relationship between genetic variation and phenotypic heterogeneity—and to explore building more accurate and representative cell-based models with which to interrogate this relationship— we propose to hold a multi-disciplinary scientific conference that connects junior and senior researchers from the genetics and genomics, cell biology, and bioinformatics fields and focuses on pluripotent stem cells as an important model for human disease, human genetic diversity, and as a potential future tool for personalized regenerative medicine. The conference will promote networking and multi-disciplinary collaboration, and will inform and train junior investigators in state-of-the-art genetic and bioinformatic approaches for conducting rigorous studies that utilize and leverage human and murine pluripotent stem cells.