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This lecture explores the role of pioneer transcription factors in binding heterochromatic DNA and activating cell fate choices. It discusses the bookmarking transcription factors that stay bound to mitotic chromosomes and the chromatin organization in pluripotent cells. The concept of bivalent chromatin domains in ES cells is also covered, along with the relationship between chromatin state and plasticity. The lecture presents a working model of how transcription factors and chromatin state define cell identity and transitions. Examples of transdifferentiation and direct reprogramming are provided, showcasing the conversion of one cell type into another using master transcription factors. The potential applications of reprogramming in regenerative medicine are discussed, highlighting the advantages and limitations of different approaches. The plasticity of adult stem cells and the influence of the environment on cell fate decisions are also examined.