Role of EMT Mediators in Differentiation of Hematopoietic Stem Cells and Interaction with the Microenvironment

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HSCs underlie a strict control between self renewal and differentiation processes to prevent exhaustion or malignant transformation. Better understanding of mechanisms that regulate hematopoietic stem cell self renewal and differentiation not only holds the promise on understanding diseases, but also may enable to explore new possibilities to use alternative sources of stem cells for regenerative medicine. During the embryonic development, the determination of cell fate is executed by transformation from epithelial to mesenchymal cell lineage, termed as EMT (epithelial to mesenchymal transition), a compelling process involving changes in cell structure, interaction with the surrounding environment and migration. Some members of transcription factor families including Snails, Zebs and Twists have been associated to play a crucial role in the EMT process. However, little is known about the physiological role of these transcription factors in regulation of hematopoietic stem cells differentiation. In this study, the collaborators between China and Germany will use human induced pluripotent stem cells and transgenic mice as in vitro and in vivo models to investigate the role of EMT-related transcription factors in differentiation of different hematopoietic lineages. Human iPSCs will be genetically modified to derive consistent knock-in/out pluripotent stem cell lines utilizing the novel TALEN approach. The transgenic animals are based on conditional deletion of the desired gene sequences which were already generated and ready to use for this study. The anticipated results of this study will provide new knowledge of the regulatory mechanism by EMT-associated transcription factors in the hematopoietic system and may lead to better utilization of stem cells in the clinical use.