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Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

Neural Regeneration Research 2025年第4期20卷 946-959页

作者： Zhiyuan Yin Jiahui Kang Xuan Cheng Hui Gao Shujia Huo Haiwei Xu Key Lab of Visual Damage and Regeneration&Restoration of Chongqing Southwest Eye HospitalSouthwest HospitalThird Military Medical University(Army Medical University)ChongqingChina

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased *** lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored ***,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various *** in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in ***,there remain issues that hinder improving reprogramming efficiency and ***,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming *** review describes recent progress in relatively successful Müller glia reprogramming *** also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

关键词： cell fusion chemical small-molecules epigenetic extracellular matrix immune metabolic mice Müller glia neurodegenerative diseases reprogramming retina regeneration

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reprogramming cell fates by small molecules

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Protein & Cell 2017年第5期8卷 328-348页

作者： Xiaojie Ma Linghao Kong Saiyong Zhu Life Sciences Institute Zhejiang University Hangzhou 310058 China

reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our under- standing of cellular plasticity. During the last decade, transcription factors and microRNAs have become powerful reprogramming factors for modulating cell fates. Recently, many efforts are focused on repro- gramming cell fates by non-viral and non-integrating chemical approaches. Small molecules not only are useful in generating desired cell types in vitro for vari- ous applications, such as disease modeling and cell- based transplantation, but also hold great promise to be further developed as drugs to stimulate patients＇ endogenous cells to repair and regenerate in vivo. Here we will focus on chemical approaches for generating induced pluripotent stem cells, neurons, cardiomy- ocytes, hepatocytes and pancreatic is cells. Significantly, the rapid and exciting advances in cellular reprogramming by small molecules will help us to achieve the long-term goal of curing devastating diseases, injuries, cancers and aging.

关键词： reprogramming small molecules stem cells cell fates

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Global epigenetic changes during somatic cell reprogramming to iPS cells

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Journal of Molecular Cell Biology 2011年第6期3卷 341-350页

作者： Anna Mattout Alva Biran Eran Meshorer Department of Genetics Institute of Life SciencesThe Hebrew University of JerusalemJerusalem 91904Israel

Embryonic stem cells(ESCs)exhibit unique chromatin features,including a permissive transcriptional program and an open,decondensed chromatin *** pluripotent stem cells(iPSCs),which are very similar to ESCs,hold great promise for therapy and basic ***,the mechanisms by which reprogramming occurs and the chromatin organization that underlies the reprogramming process are largely *** we characterize and compare the epigenetic landscapes of partially and fully reprogrammed iPSCs to mouse embryonic fibroblasts(MEFs)and ESCs,which serves as a standard for *** immuno-fluorescence and biochemical fractionations,we analyzed the levels and distribution of a battery of histone modifications(H3ac,H4ac,H4K5ac,H3K9ac,H3K27ac,H3K4me3,H3K36me2,H3K9me3,H3K27me3,and gH2AX),as well as HP1a and lamin *** find that fully reprogrammed iPSCs are epigenetically identical to ESCs,and that partially reprogrammed iPSCs are closer to ***,combining both time-course reprogramming experiments and data from the partially reprogrammed iPSCs,we find that heterochromatin reorganization precedes Nanog expression and active histone ***,these data delineate the global epigenetic state of iPSCs in conjunction with their pluripotent state,and demonstrate that heterochromatin precedes euchromatin in reorganization during reprogramming.

关键词： chromatin pluripotency reprogramming iPSCs ESCs histone modifications epigenetics

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reprogramming of germ cells into pluripotency

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World Journal of Stem Cells 2016年第8期8卷 251-259页

作者： Yoichi Sekita Toshinobu Nakamura Tohru Kimura Laboratory of Stem Cell Biology Department of Biosciences Kitasato University School of Science Laboratory of Epigenetic Regulation Department of Animal Bioscience Nagahama Institute of Bio-Science and Technology

Primordial germ cells(PGCs) are precursors of all gametes, and represent the founder cells of the germline. Although developmental potency is restricted to germ-lineage cells, PGCs can be reprogrammed into a pluripotent state. Specifically, PGCs give rise to germ cell tumors, such as testicular teratomas, in vivo, and to pluripotent stem cells known as embryonic germ cells in vitro. In this review, we highlight the current knowledge on signaling pathways, transcriptional controls, and post-transcriptional controls that govern germ cell differentiation and de-differentiation. These regulatory processes are common in the reprogramming of germ cells and somatic cells, and play a role in the pathogenesis of human germ cell tumors.

关键词： Primordial germ cell Embryonic germ cell Germ cell tumor reprogramming Induced pluripotent stem cell Small molecule compound Gene Signal Transcription factor

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Repressors of reprogramming

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World Journal of Stem Cells 2015年第3期7卷 541-546页

作者： Melissa Popowski Haley Tucker the Rockefeller University New York Institute for Cellular and Molecular Biology University of Texas at Austin

Induced pluripotent stem cells(i PSCs) have been the focal point of ever increasing interest and scrutiny as they hold the promise of personalized regenerative medicine. However, creation of i PSCs is an inefficient process that requires forced expression of potentially oncogenic proteins. In order to unlock the full potential of i PSCs, both for basic and clinical research, we must broaden our search for more reliable ways of inducing pluripotency in somatic cells. This review surveys an area of reprogramming that does not receive as much focus, barriers to reprogramming, in the hope of stimulating new ideas and approaches towardsdeveloping safer and more efficient methods of reprogramming. Better methods of i PSC creation will allow for more reliable disease modeling, better basic research into the pluripotent state and safer i PSCs that can be used in a clinical setting.

关键词： reprogramming Induced pluripotency Stem cells

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Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis

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National Science Review 2019年第5期6卷 993-1003页

作者： Xiaocui Xu Guoqiang Li Congru Li Jing Zhang Qiang Wang David K.Simmons Xuepeng Chen Naveen Wijesena Wei Zhu Zhanyang Wang Zhenhua Wang Bao Ju Weimin Ci Xuemei Lu Daqi Yu Qian-fei Wang Neelakanteswar Aluru Paola Oliveri Yong E.Zhang Mark Q.Martindale Jiang Liu CAS Key Laboratory of Genome Sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences University of Chinese Academy of Sciences Institute of Apiculture Research Chinese Academy of Agriculture Sciences Whitney Laboratory for Marine Bioscience University of Florida College of Life Sciences Yantai University CAS Key Laboratory of Genomics and Precision Medicine Beijing Institute of Genomics Chinese Academy of Sciences Institute of Zoology Chinese Academy of Sciences Biology Department Woods Hole Oceanographic Institution Departments of Genetics Evolution and Environment and Cell and Developmental Biology University College London CAS Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

Major evolutionary transitions are enigmas, and the most notable enigma is between invertebrates and vertebrates, with numerous spectacular *** search for the molecular connections involved, we asked whether global epigenetic changes may offer a clue by surveying the inheritance and reprogramming of parental DNA methylation across *** focused on gametes and early embryos, where the methylomes are known to evolve divergently between fish and ***, we find that methylome reprogramming during embryogenesis occurs neither in pre-bilaterians such as cnidarians nor in protostomes such as insects, but clearly presents in deuterostomes such as echinoderms and invertebrate chordates, and then becomes more evident in *** association analysis suggests that DNA methylation reprogramming is associated with development, reproduction and adaptive immunity for vertebrates, but not for ***, the single HOX cluster of invertebrates maintains unmethylated status in all stages *** contrast, the multiple HOX clusters show dramatic dynamics of DNA methylation during vertebrate ***, the methylation dynamics of HOX clusters are associated with their spatiotemporal expression in *** study reveals that DNA methylation reprogramming has evolved dramatically during animal evolution, especially after the evolutionary transitions from invertebrates to vertebrates, and then to mammals.

关键词： DNA methylation evolution development reprogramming

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Transposable elements at the center of the crossroads between embryogenesis, embryonic stem cells, reprogramming,and long non-coding RNAs

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Science Bulletin 2015年第20期60卷 1722-1733页

作者： Andrew Paul Hutchins Duanqing Pei Key Laboratory of Regenerative Biology South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou Branch of the Supercomputing Center of Chinese Academy of Sciences South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences

Transposable elements(TEs) are mobile genomic sequences of DNA capable of autonomous and nonautonomous duplication. TEs have been highly successful,and nearly half of the human genome now consists of various families of TEs. Originally thought to be non-functional,these elements have been co-opted by animal genomes to perform a variety of physiological functions ranging from TE-derived proteins acting directly in normal biological functions, to innovations in transcription factor logic and influence on epigenetic control of gene expression. During embryonic development, when the genome is epigenetically reprogrammed and DNA-demethylated, TEs are released from repression and show embryonic stage-specific expression, and in human and mouse embryos, intact TEderived endogenous viral particles can even be detected. Asimilar process occurs during the reprogramming of somatic cells to pluripotent cells: When the somatic DNA is demethylated, TEs are released from repression. In embryonic stem cells(ESCs), where DNA is hypomethylated, an elaborate system of epigenetic control is employed to suppress TEs, a system that often overlaps with normal epigenetic control of ESC gene expression. Finally, many long non-coding RNAs(lnc RNAs) involved in normal ESC function and those assisting or impairing reprogramming contain multiple TEs in their RNA. These TEs may act as regulatory units to recruit RNA-binding proteins and epigenetic modifiers. This review covers how TEs are interlinked with the epigenetic machinery and lnc RNAs, and how these links influence each other to modulate aspects of ESCs,embryogenesis, and somatic cell reprogramming.

关键词： Transposable elements Endogenousretroviruses Embryonic stem cells lncRNA reprogramming Pluripotency

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Intrinsic fluctuation and susceptibility in somatic cell reprogramming process

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Chinese Physics B 2019年第4期28卷 113-120页

作者： Jian Shen Xiaomin Zhang Qiliang Li Xinyu Wang Yunjie Zhao Ya Jia Department of Physics Central China Normal University School of Information Engineering Wuhan Technology and Business University

Based on the coherent feedforward transcription regulation loops in somatic cell reprogramming process, a stochastic kinetic model is proposed to study the intrinsic fluctuations in the somatic cell reprogramming. The Fano factor formulas of key genes expression level in the coherent feedforward transcription regulation loops are derived by using of Langevin theory. It is found that the internal fluctuations of gene expression levels mainly depend on itself activation ratio and degradation ratio. When the self-activation ratio(or self-degradation ratio) is increased, the Fano factor increases reaches a maximum and then decreases. The susceptibility is used to measure the sensitivity of steady-state response to the variation in systemic parameters. It is found that with the increase of the self-activation ratio(or self-degradation ratio), the susceptibility of steady-state increases at first, it reaches a maximum, and it then decreases. The magnitude of the maximum is increased with the increase of activated ratio by the upstream transcription factor.

关键词： intrinsic fluctuation susceptibility coherent feedforward loops somatic cell reprogramming

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In vivo astrocyte-to-neuron reprogramming for central nervous system regeneration:a narrative review

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Neural Regeneration Research 2023年第4期18卷 750-755页

作者： Zuliyaer Talifu Jia-Yi Liu Yun-Zhu Pan Han Ke Chun-Jia Zhang Xin Xu Feng Gao Yan Yu Liang-Jie Du Jian-Jun Li School of Rehabilitation Capital Medical UniversityBeijingChina Department of Spinal and Neural Functional Reconstruction China Rehabilitation Research CenterBeijingChina Chinese Institute of Rehabilitation Science BeijingChina Center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina Beijing Key Laboratory of Neural Injury and Rehabilitation BeijingChina School of Rehabilitation Sciences and Engineering University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

The inability of damaged neurons to regenerate within the mature central nervous system(CNS)is a significant neuroscientific *** are an essential component of the CNS and participate in many physiological processes including blood-brain barrier formation,axon growth regulation,neuronal support,and higher cognitive functions such as *** reprogramming studies have confirmed that astrocytes in the mature CNS can be transformed into functional *** on in vitro work,many studies have demonstrated that astrocytes can be transformed into neurons in different disease models to replace damaged or lost ***,many findings in this field are controversial,as the source of new neurons has been *** review summarizes progress in reprogramming astrocytes into neurons in vivo in animal models of spinal cord injury,brain injury,Huntington’s disease,Parkinson’s disease,Alzheimer’s disease,and other neurodegenerative conditions.

关键词： astrocyte astrocyte-to-neuron central nervous system in vivo nerve regeneration neurological disorders reprogramming review

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Identification of potential candidate proteins for reprogramming spinal cord-derived astrocytes into neurons:a proteomic analysis

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Neural Regeneration Research 2021年第11期16卷 2257-2263页

作者： Wen-Hao Chen Yu-Xiang Lin Ling Lin Bao-Quan Zhang Shu-Xia Xu Wei Wang Department of Pediatric Surgery Fujian Maternity and Child Health HospitalAffiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Breast Surgery Affiliated Union HospitalFujian Medical UniversityFuzhouFujian ProvinceChina Institutes of Biomedical Sciences of Shanghai Medical School Fudan UniversityShanghaiChina Department of Neonatology Fujian Maternity and Child Health HospitalAffiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Pathology Fujian Maternity and Child Health HospitalAffiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Anatomy and Histoembryology Fujian Medical UniversityFuzhouFujian ProvinceChina

Our previous study has confirmed that astrocytes overexpressing neurogenic differentiation factor 1(NEUROD1)in the spinal cord can be reprogrammed into neurons under in vivo ***,whether they can also be reprogrammed into neurons under in vitro conditions remains unclear,and the mechanisms of programmed conversion from astrocytes to neurons have not yet been *** the present study,we prepared reactive astrocytes from newborn rat spinal cord astrocytes using the scratch method and infected them with lentivirus carrying *** results showed that NEUROD1 overexpression reprogrammed the cultured reactive astrocytes into neurons in vitro with an efficiency of 13.4%.Using proteomic and bioinformatic analyses,1952 proteins were identified,of which 92 were differentially *** these proteins,11 were identified as candidate proteins in the process of reprogramming based on their biological functions and fold-changes in the bioinformatic ***,western blot assay revealed that casein kinase II subunit alpha(CSNK2A2)and pinin(PNN)expression in NEUROD1-overexpressing reactive astrocytes was significantly increased,suggesting that NEUROD1 can directly reprogram spinal cord-derived reactive astrocytes into neurons in vitro,and that the NEUROD1-CSNK2A2-PNN pathway is involved in this *** study was approved by the Animal Ethics Committee of Fujian Medical University,China(approval No.2016-05)on April 18,2016.

关键词： astrocytes glial cells label-free proteomic analysis mechanism neurons primary culture reprogramming spinal cord injury

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