Reprogramming of somatic cells to induced pluripotent stem cells （iPSCs） is a comprehensive epigenetic process involving genome-wide modifications of histones and DNA methylation. This process is often incomplete, w...Reprogramming of somatic cells to induced pluripotent stem cells （iPSCs） is a comprehensive epigenetic process involving genome-wide modifications of histones and DNA methylation. This process is often incomplete, which subsequently affects iPSC reprograming, pluripotency, and differentiation capacity. Here, we review the epigenetic changes with a focus on histone modification （methylation and acetylation） and DNA modification （methylation） during iPSC induction. We look at changes in specific epigenetic signatures, aberrations and epigenetic memory during reprogramming and small molecules influencing the epigenetic reprogramming of somatic cells. Finally, we discuss how to improve iPSC generation and pluripotency through epigenetic manipulations.展开更多
How cells sense and respond to environmental changes is still a key question.It has been identified that cellular metabolism is an important modifier of various epigenetic modifications,such as DNA methylation,histone...How cells sense and respond to environmental changes is still a key question.It has been identified that cellular metabolism is an important modifier of various epigenetic modifications,such as DNA methylation,histone methylation and acetylation and RNA N6-methyladenosine(m6A)methylation.This closely links the environmental nutrient availability to the maintenance of chromatin structure and gene expression,and is crucial to regulate cellular homeostasis,cell growth and differentiation.Cancer metabolic reprogramming and epigenetic alterations are widely observed,and facilitate cancer development and progression.In cancer cells,oncogenic signaling-driven metabolic reprogramming modifies the epigenetic landscape via changes in the keymetabolite levels.In this review,we briefly summarized the current evidence that the abundance of key metabolites,such as S-adenosyl methionine(SAM),acetyl-CoA,α-ketoglutarate(α-KG),2-hydroxyglutarate(2-HG),uridine diphospho-N-acetylglucosamine(UDP-GlcNAc)and lactate,affected by metabolic reprogramming plays an important role in dynamically regulating epigenetic modifications in cancer.An improved understanding of the roles of metabolic reprogramming in epigenetic regulation can contribute to uncover the underlying mechanisms of metabolic reprogramming in cancer development and identify the potential targets for cancer therapies.展开更多
Mammalian fertilization begins with the fusion of two specialized gametes,followed by major epigenetic remodeling leading to the formation of a totipotent embryo.During the development of the pre-implantation embryo,p...Mammalian fertilization begins with the fusion of two specialized gametes,followed by major epigenetic remodeling leading to the formation of a totipotent embryo.During the development of the pre-implantation embryo,precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality,but the underlying molecular mechanisms remain elusive.For the past few years,unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development,taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies.The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals,including DNA methylation,histone modifications,chromatin accessibility and 3D chromatin organization.展开更多
基金supported by the Lundbeck Foundation(No.R151-2013-14439)the Danish Research Council for Independent Research(No.16942)
文摘Reprogramming of somatic cells to induced pluripotent stem cells （iPSCs） is a comprehensive epigenetic process involving genome-wide modifications of histones and DNA methylation. This process is often incomplete, which subsequently affects iPSC reprograming, pluripotency, and differentiation capacity. Here, we review the epigenetic changes with a focus on histone modification （methylation and acetylation） and DNA modification （methylation） during iPSC induction. We look at changes in specific epigenetic signatures, aberrations and epigenetic memory during reprogramming and small molecules influencing the epigenetic reprogramming of somatic cells. Finally, we discuss how to improve iPSC generation and pluripotency through epigenetic manipulations.
基金National Natural Science Foundation of China(91749205,92049302,32088101)China Ministry of Science and Technology(2020YFA0804000,2016YFE0108700)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)to J.D.J.H.The funding organizations played no role in the study design。
文摘How cells sense and respond to environmental changes is still a key question.It has been identified that cellular metabolism is an important modifier of various epigenetic modifications,such as DNA methylation,histone methylation and acetylation and RNA N6-methyladenosine(m6A)methylation.This closely links the environmental nutrient availability to the maintenance of chromatin structure and gene expression,and is crucial to regulate cellular homeostasis,cell growth and differentiation.Cancer metabolic reprogramming and epigenetic alterations are widely observed,and facilitate cancer development and progression.In cancer cells,oncogenic signaling-driven metabolic reprogramming modifies the epigenetic landscape via changes in the keymetabolite levels.In this review,we briefly summarized the current evidence that the abundance of key metabolites,such as S-adenosyl methionine(SAM),acetyl-CoA,α-ketoglutarate(α-KG),2-hydroxyglutarate(2-HG),uridine diphospho-N-acetylglucosamine(UDP-GlcNAc)and lactate,affected by metabolic reprogramming plays an important role in dynamically regulating epigenetic modifications in cancer.An improved understanding of the roles of metabolic reprogramming in epigenetic regulation can contribute to uncover the underlying mechanisms of metabolic reprogramming in cancer development and identify the potential targets for cancer therapies.
基金This work was supported by the National Key R&D Program of China(2016YFA0100400 and 2018YFC1004000)and the National Natural Science Foundation of China(31721003,31820103009,31701262,81630035).
文摘Mammalian fertilization begins with the fusion of two specialized gametes,followed by major epigenetic remodeling leading to the formation of a totipotent embryo.During the development of the pre-implantation embryo,precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality,but the underlying molecular mechanisms remain elusive.For the past few years,unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development,taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies.The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals,including DNA methylation,histone modifications,chromatin accessibility and 3D chromatin organization.
