Mediator 1 Ablation Induces Enamel-to-Hair Lineage Conversion Through Enhancer Dynamics

    September 2022 in “ bioRxiv (Cold Spring Harbor Laboratory) ”
    Roman Thaler, Keigo Yoshizaki, Thai Nguyen, Satoshi Fukumoto, Pamela DenBesten, Daniel Bikle, Yuko Oda
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    TLDR Removing Mediator 1 causes teeth cells to turn into hair cells.
    The study found that Mediator 1 (Med1), a key component of the Mediator complex that links enhancer activities to gene transcription, plays a crucial role in determining tissue-specific lineage commitment and progression of dental epithelia. When Med1 is deleted, it causes a shift in lineage, leading to hair growth in the dental environment. This unusual hair growth occurs via primitive cellular aggregates on incisors. Med1 establishes super-enhancers that control enamel lineage transcription factors in dental stem cells and their progenies. However, its deficiency reshapes the enhancer landscapes and causes a switch from the dental epithelial transcriptional program towards hair and epidermis on incisors in vivo, and in dental epithelial stem cells in vitro. The study suggests that Med1 safeguards lineage-specific enhancers and plays a central role in lineage reprogramming, providing new insights into ectodermal regeneration.
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