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MINI REVIEW article

Front. Cell Dev. Biol.

Sec. Stem Cell Research

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1559183

This article is part of the Research Topic External Factors Influencing Stem Cells’ Pluripotency, Senescence, and Differentiation View all 7 articles

Epigenetic Regulation of Reprogramming and Pluripotency: Insights from Histone Modifications and Their Implications for Cancer Stem Cell Therapies

Provisionally accepted
Woori Bae Woori Bae 1*Eun A Ra Eun A Ra 2*Myon Hee Lee Myon Hee Lee 3*
  • 1 Department of Biochemistry and Molecular Pharmacology, Grossman School of Medicine, New York University, New York, New York, United States
  • 2 Institute for Cell Engineering, School of Medicine, Johns Hopkins Medicine, Baltimore, Maryland, United States
  • 3 Brody School of Medicine, East Carolina University, Greenville, United States

The final, formatted version of the article will be published soon.

    Pluripotent stem cells (PSCs) possess the extraordinary capability to differentiate into a variety of cell types. This capability is tightly regulated by epigenetic mechanisms, particularly histone modifications. Moreover, the reprogramming of somatic or fate-committed cells into induced pluripotent stem cells (iPSCs) largely relies on these modifications, such as histone methylation and acetylation of histones. While extensive research has been conducted utilizing mouse models, the significance of histone modifications in human iPSCs is gaining increasing recognition. Recent studies underscore the importance of epigenetic regulators in both the reprogramming process and the regulation of cancer stem cells (CSCs), which are pivotal in tumor initiation and the development of treatment resistance. This review elucidates the dynamic alterations in histone modifications that impact reprogramming and emphasizes the necessity for a balance between activating and repressive marks. These epigenetic marks are influenced by enzymes such as DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). Furthermore, this review explores therapeutic strategies aimed at targeting these epigenetic modifications to enhance treatment efficacy in cancer while advancing the understanding of pluripotency and reprogramming. Despite promising developments in the creation of inhibitors for histone-modifying enzymes, challenges such as selectivity and therapy resistance continue to pose significant hurdles. Therefore, future endeavors must prioritize biomarker-driven approaches and gene-editing technologies to optimize the efficacy of epigenetic therapies.

    Keywords: pluripotent stem cells (PSCs), Histone Modifications, Epigenetic regulations, cancer stem cells, reprogramming

    Received: 12 Jan 2025; Accepted: 13 Feb 2025.

    Copyright: © 2025 Bae, Ra and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Woori Bae, Department of Biochemistry and Molecular Pharmacology, Grossman School of Medicine, New York University, New York, NY 10016, New York, United States
    Eun A Ra, Institute for Cell Engineering, School of Medicine, Johns Hopkins Medicine, Baltimore, MD 21205-1832, Maryland, United States
    Myon Hee Lee, Brody School of Medicine, East Carolina University, Greenville, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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