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Unraveling brain aging through the lens of oral microbiota

Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina institute for stem cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing institute for stem cell and regenerative medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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Single-cell technologies: current and near future

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Science china Life Sciences 2025年第1期68卷 1-4页

作者： Chenfei Wang Qi Liu Xiaohui Fan Tieliu Shi Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration Ministry of EducationOrthopedics DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for stem cells School of Life Sciences and TechnologyTongji University Translational Medical Center for stem cell Therapy and institute for regenerative medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research institute of Intelligent Computing Zhejiang Lab Pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang University National Key Laboratory of Chinese medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Key Laboratory of Advanced Theory and Application in Statistics and Data Science (MOE) School of StatisticsEast China Normal University

Single-cell technologies enable the indepth exploration of multiple biological hierarchies at the scale of individual cells,which have deepened our knowledge of cellular diversity, tissue organization, and overall organism function(Sun et al.,2024). In 2009, single-cell RNA sequencing(sc RNA-seq) was first developed as a powerful tool to dissect gene expression and uncover transcriptional *** the rapid advancement of technology, single-cell approaches have expanded to encompass other omics, such as genomics, epigenomics, proteomics,and metabolomics.

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Single-cell omics: experimental workflow, data analyses and applications

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Science china Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for stem cells School of Life Sciences and TechnologyTongji University Translational Medical Center for stem cell Therapy and institute for regenerative medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research institute of Intelligent Computing Zhejiang Lab Shanghai Research institute for Intelligent Autonomous Systems Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

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Role of Lef1 in sustaining self-renewal in mouse embryonic stem cells

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Journal of Genetics and Genomics 2010年第7期37卷 441-449页

作者： Chen Huang Dajiang Qin stem cell and Cancer biology Group Key Laboratory of Regenerative Biology South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institute of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510530 China

Embryonic stem cells （ESCs） can self-renew indefinitely while maintaining the ability to generate all three germ-layer *** the importance of ESCs in developmental biology and their potential impact on regenerative medicine,the molecular mechanisms controlling ESC behavior are incompletely ***,activation of the canonical Wnt signaling pathway has been shown to contribute to mouse ESC *** we report that ectopic expression of Lef1,a component of the Wnt signaling pathway,has a positive effect on the self-renewal of mouse ***1 up-regulates Oct4 promoter activity and physically interacts with Nanog,two key components of the ESC pluripotency ***,siRNA for Lef1 induced mouse ESC *** results thus suggest that in response to Wnt signaling Lef1 binds to stabilized β-catenin and helps maintain the undifferentiated status of ESCs through modulation of Oct4 and Nanog.

关键词： embryonic stem cells Wnt signaling 13-catenin Lefl Oct4 Nanog

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Current approaches to reduce or eliminate mitochondrial DNA mutations

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Science china(Life Sciences) 2016年第5期59卷 532-535页

作者： Liang Yang Tingfang Mei Xiaobing Lin Haite Tang Yi Wu Rui Wang Jinglei Liu Zahir Shah Xingguo Liu Key Laboratory of regenerative biology 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

Mitochondrial DNA （mtDNA） mutations have been impli- cated in a broad range of disorders which severely affect human health （Wallace, 1999）. Some drugs have been developed to slow down pathological changes of mitochon- drial disorders. However, there is no effective treatment for patients with mtDNA mutations, mtDNA is less protected and has fewer repair mechanisms than nuclear DNA （nDNA）. Such a reality results in a much higher mutation rate in mtDNA than that in nDNA. The mixture of mutated mtDNA versus wild-type mtDNA is known as hetero- plasmy. Mitochondrial threshold effect refers to the fact that mtDNA mutation must accumulate to high proportions （60%-90%） before respiratory activity is affected （Schon et al., 2012）. It is feasible to selectively reduce the levels of mu- tated mtDNA while sparing wild-type mtDNA to skew this ratio back to a healthier range. Here, we describe the link between mtDNA mutation and mitochondrial diseases, and we summarize several newly developed approaches with regard to the reduction or elimination of mtDNA mutation in mammals. These methods include nuclear gene modula- tion, molecular approaches targeting mutated mtDNA, mtDNA replacement, and induced pluripotent stem cell （iPSC） modeling. These various methods have their own advantages and limitations.

关键词：线粒体DNA突变基因突变 mtDNA突变线粒体疾病人类健康核DNA 多能干细胞病理变化

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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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Induced pluripotent stem cell (iPS) technology:promises and challenges

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Chinese Science Bulletin 2009年第1期54卷 2-8页

作者： MIGUEL A Esteban Laboratory of regenerative biology South China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institute of Biomedicine and HealthChinese Academy of Sciences

In 2006,an article published in cell by Shinya Yamanaka took by surprise the stem cell research community. By performing systematic retroviral transduction of factors enriched in embryonic stem (ES) cells,the authors demonstrated the reprogramming of mouse fibroblasts into an ES cell-like state. These cells,baptized iPS (induced pluripotent stem) cells,were immediately recognized as a ground-breaking discovery. Subsequently,the same authors and other groups reported a similar achievement with human fibroblasts. Two years later,the number of top quality papers on iPS is astonishing,and interest in the scientific community has risen to a fever pitch. But although iPS has the potential to revolutionize regenerative medicine,important questions still remain unanswered. Work from multiple laboratories worldwide including ours is focused on deciphering the molecular mechanisms of iPS,and trying to improve the technique to make it suitable for the clinic. In this review article we briefly discuss the past,present and future of iPS,with emphasis on urgent issues to be solved.

关键词：自身更新多能性胚胎干细胞多能干细胞

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Effective gene targeting in rabbits using RNA-guided Cas9 nucleases

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Journal of Molecular cell biology 2014年第1期8卷 97-99页

作者： Dongshan Yang Jie Xu Tianqing Zhu Jianglin Fan Liangxue Lai Jifeng Zhang Y. Eugene Chen southern china institute of stem cell biology and regenerative medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou China

Dear Editor, Recently, zinc finger nuclease, transcrip- tion activator-like effector nuclease, and RNA-guided Cas9 endonuciease （Cas9） have emerged as powerful means for genome editing （Conklin, 2013; Gaj eta[., 2013）. These nucleases are efficient in gen- erating double-strand breaks in the genome that can be repaired by error-prone nonho- mologous end joining leading to a functional knockout （KO） of the targeted gene or used to integrate a DNA sequence at a specific locus through homologous recombination.

关键词：核酸酶基因组 RNA 制导同源重组 DNA序列转录激活双链断裂

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EMT and MET as paradigms for cell fate switching

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Journal of Molecular cell biology 2012年第2期4卷 66-69页

作者： Jiekai Chen Qingkai Han Duanqing Pei Key Laboratory of regenerative biology South China Institute for Stem Cell Biology and Regenerative Medicine at Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China

cell fate determination is a major unsolved problem in cell and developmental *** discovery of reprogramming by pluri-potent factors offers a rational system to investigate the molecular mechanisms associated with cell fate *** idea that reprogramming of fibroblasts starts with a mesenchymal-epithelial transition(MET)suggests that the process is perhaps a reversal of epithelial to mesenchymal transition(EMT)found frequently during early *** such,we believe that investigations into MET-EMT may yield detailed molecular insights into cell fate decisions,not only for the switching between epithelial and mesenchymal cells,but also other cell types.

关键词： EMT programming rational

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Programmable synthetic receptors:the next-generation of cell and gene therapies

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Signal Transduction and Targeted Therapy 2024年第2期9卷 376-400页

作者： Fei Teng Tongtong Cui Li Zhou Qingqin Gao Qi Zhou Wei Li University of Chinese Academy of Sciences Beijing 101408China State Key Laboratory of stem cell and regenerative biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing institute for stem cell and regenerative medicine Beijing 100101China

cell and gene therapies hold tremendous promise for treating a range of difficult-to-treat ***,concerns over the safety and efficacy require to be further addressed in order to realize their full *** receptors,a synthetic biology tool that can precisely control the function of therapeutic cells and genetic modules,have been rapidly developed and applied as a powerful *** designed and engineered,they can be applied to finetune the therapeutic activities,i.e.,to regulate production of dosed,bioactive payloads by sensing and processing user-defined signals or *** review provides an overview of diverse synthetic receptor systems being used to reprogram therapeutic cells and their wide applications in biomedical *** a special focus on four synthetic receptor systems at the forefront,including chimeric antigen receptors(CARs)and synthetic Notch(synNotch)receptors,we address the generalized strategies to design,construct and improve synthetic ***,we also highlight the expanding landscape of therapeutic applications of the synthetic receptor systems as well as current challenges in their clinical translation.

关键词： synthetic landscape payload

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