Tailored Chromatin Modulation to Promote Tissue Regeneration

    Paloma Martínez-Redondo, Juan Carlos Izpisüa Belmonte
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    TLDR Understanding and manipulating epigenetic changes can potentially lead to human organ regeneration therapies, but more research is needed to improve these methods and minimize risks.
    The document from January 1, 2020, reviews the role of epigenetic regulation in tissue regeneration, highlighting the importance of DNA methylation, histone modifications, and chromatin remodeling in cellular processes such as de-differentiation, proliferation, and re-differentiation. It discusses the regenerative abilities of lower vertebrates and the limited regeneration in mammals, which declines with age, but suggests that the mechanisms for regeneration exist and may become inactive in adulthood. The review details the role of epigenetic mechanisms in controlling gene expression during regeneration and the potential of CRISPR-based editing technologies to study and promote tissue regeneration. It emphasizes the need for a balance of epigenetic modifiers in stem cell maintenance and differentiation, citing the importance of Polycomb repressive complexes, DNA methylation, and histone modifications in various types of stem cells, including HSCs, MuSCs, NSCs, ISCs, and EPCs. The document also discusses the potential of CRISPR/Cas9-based chromatin modification systems to target specific genomic loci or regulate gene expression, despite the current limitations such as off-target effects. Overall, the document concludes that understanding epigenetic changes that promote regeneration could lead to therapies for regenerating organs in humans, but more research is needed to enhance the effectiveness of these technologies and reduce risks.
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