Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies

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...

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Main Authors: Woori Bae, Eun A. Ra, Myon Hee Lee
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1559183/full
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author Woori Bae
Eun A. Ra
Eun A. Ra
Myon Hee Lee
author_facet Woori Bae
Eun A. Ra
Eun A. Ra
Myon Hee Lee
author_sort Woori Bae
collection DOAJ
description 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.
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spelling doaj-art-a675a769ec1b4308899211fdc4b19fa42025-08-20T02:00:47ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-03-011310.3389/fcell.2025.15591831559183Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapiesWoori Bae0Eun A. Ra1Eun A. Ra2Myon Hee Lee3Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, United StatesInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Medicine, Hematology/Oncology Division, Brody School of Medicine at East Carolina University, Greenville, NC, United StatesPluripotent 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.https://www.frontiersin.org/articles/10.3389/fcell.2025.1559183/fullpluripotent stem cells (PSCs)histone modificationsepigenetic regulationscancer stem cellsreprogramming
spellingShingle Woori Bae
Eun A. Ra
Eun A. Ra
Myon Hee Lee
Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies
Frontiers in Cell and Developmental Biology
pluripotent stem cells (PSCs)
histone modifications
epigenetic regulations
cancer stem cells
reprogramming
title Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies
title_full Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies
title_fullStr Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies
title_full_unstemmed Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies
title_short Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies
title_sort epigenetic regulation of reprogramming and pluripotency insights from histone modifications and their implications for cancer stem cell therapies
topic pluripotent stem cells (PSCs)
histone modifications
epigenetic regulations
cancer stem cells
reprogramming
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1559183/full
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