Role of Pluripotency Factors in Pluripotent Stem Cells, Development and Disease

National Institute Of Environmental Health Sciences

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Abstract

Pluripotent stem cells can be used as cell culture models to study the molecular basis of pluripotency and fate-specification during early mammalian development. They can also be used to derive various types of cells for disease modeling, drug discovery, and cell-based therapies. However, the success of these studies and applications critically depends on the understanding of the mechanisms that control the pluripotent state in the stem cells. To systematically study the pluripotent state, we are using genetic and genomic approaches in cultured cells and animal models to identify and characterize genes and pathways that are important for stem cell self-renewal and differentiation. We are currently investigating the roles of the INO80 chromatin remodeling and Ccr4-Not mRNA deadenylation complexes in the transcriptional and post-transcriptional gene regulation in pluripotency, early development, and disease. In addition, we are developing new genetic and genomic tools to further study the establishment, maintenance, and resolution of the pluripotent state. Finally, we are using stem cells as an in vitro model to study the developmental toxicity of environmental compounds to better understand the impact of environmental factors on human health and diseases. We believe that our studies will provide new insights to stem cell and developmental biology, and advance environmental health science and translational research with stem cell based new approach methodologies.