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FHL2 deficiency aggravates Candida albicans infection through decreased myelopoiesis

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Science China Life Sciences 2025年

作者： Rongmei Gao Kanchao Chen Yimin Wang Rongxia Guo Xiaoyu Zhang Peng Wu Weili Wang Qingxiang Huang Xuemei Xie Shangda Yang Yanling Lü Qian Ren Fei Liu Song Chen Fengxia Ma Tao Cheng Hui Cheng State key laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College CAMS Center for stem cell medicine PUMC Department of Stem Cell and Regenerative Medicine

Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation, which is crucial for maintaining homeostasis. Acute infections can prompt a hematopoietic response known as emergency myelopoiesis. In this study, using a Candida albicans (C. albicans) infection model, we demonstrated for the first time that disruption of Fhl2 led to increased fungal burden,heightened inflammatory response and reduced survival rates. Impaired myeloid hematopoiesis and immune cell production were evident, as proved by the decreased numbers of hematopoietic stem and progenitor cells (HSPCs) and granulocytes in the bone marrow of Fhl2-deficient mice. In conclusion, FHL2 regulated emergency myelopoiesis in response to C. albicans, affecting the host’s defense against pathogens.

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Advances and applications in single-cell and spatial genomics

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Science China Life Sciences 2025年

作者： Jingjing Wang Fang Ye Haoxi Chai Yujia Jiang Teng Wang Xia Ran Qimin Xia Ziye Xu Yuting Fu Guodong Zhang Hanyu Wu Guoji Guo Hongshan Guo Yijun Ruan Yongcheng Wang Dong Xing Xun Xu Zemin Zhang Beijing Advanced Innovation Center for Genomics (ICG) Peking University Guangdong Provincial key laboratory of Genome Read and Write BGI Research Bone Marrow Transplantation Center of the First Affiliated Hospital & Liangzhu laboratory Zhejiang University School of Medicine Life Sciences Institute and The Second Affiliated Hospital Zhejiang University BGI Research Biomedical Pioneering Innovation Center (BIOPIC) and School of Life Sciences Peking University Academy for Advanced Interdisciplinary Studies Peking University Institute of Hematology Zhejiang University Department of laboratory medicine of The First Affiliated Hospital & Liangzhu laboratory Zhejiang University School of Medicine Center for stem cell and regenerative medicine Zhejiang University School of Medicine Zhejiang Provincial key Lab for Tissue Engineering and regenerative medicine Dr.Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine

The applications of single-cell and spatial technologies in recent times have revolutionized the present understanding of cellular states and the cellular heterogeneity inherent in complex biological systems. These advancements offer unprecedented resolution in the examination of the functional genomics of individual cells and their spatial context within tissues. In this review, we have comprehensively discussed the historical development and recent progress in the field of single-cell and spatial genomics. We have reviewed the breakthroughs in single-cell multi-omics technologies, spatial genomics methods, and the computational strategies employed toward the analyses of singlecell atlas data. Furthermore, we have highlighted the advances made in constructing cellular atlases and their clinical applications,particularly in the context of disease. Finally, we have discussed the emerging trends, challenges, and opportunities in this rapidly evolving field.

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Unraveling brain aging through the lens of oral microbiota

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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

Transient chemical-mediated epigenetic modulation confers unrestricted lineage potential on human primed pluripotent stem cells

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Science China Life Sciences 2025年

作者： Shi Chen Yuanyuan He Lejun Lv Bei Liu Cheng Li Hongkui Deng Jun Xu Department of cell Biology School of Basic Medical Sciences Peking University Stem Cell Research Center Peking University Health Science Center Peking University Academy of Advanced Interdisciplinary Studies Peking University Beicell Therapeutics School of Life Sciences Center for Bioinformatics Center for Statistical Science Peking University MOE Engineering Research Center of regenerative medicine School of Basic Medical Sciences State Key Laboratory of Natural and Biomimetic Drugs Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation College of Life Sciences Peking-Tsinghua Center for Life Sciences Peking University

Human primed pluripotent stem cells are capable of generating all the embryonic ***,their extraembryonic trophectoderm potentials are *** remains unclear how to expand their developmental potential to trophectoderm *** we show that transient treatment with a cocktail of small molecule epigenetic modulators imparts trophectoderm lineage potentials to human primed pluripotent stem cells while preserving their embryonic *** chemically treated cells can generate trophectoderm-like cells and downstream trophoblast stem cells,diverging into syncytiotrophoblast and extravillous trophoblast *** and CUT&Tag analyses reveal that these induced cells share transcriptional profiles with in vivo trophectoderm and cytotrophoblast,and exhibit reduced H3K27me3 modification at gene loci specific to trophoblast lineages compared with primed pluripotent *** exploration highlighted the critical roles of epigenetic modulators HDAC2,EZH1/2,and KDM5s in the activation of trophoblast lineage *** findings demonstrate that transient epigenetic resetting activates unrestricted lineage potential in human primed pluripotent stem cells,and offer new mechanistic insights into human trophoblast lineage specification and in vitro models for studying placental development and related disorders.

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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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Deubiquitylating Nanog:novel role of USP21 in embryonic stem cell maintenance

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Signal Transduction and Targeted Therapy 2017年第1期2卷 239-241页

作者： Duanqing Pei key laboratory of regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of Sciences 510530Guangzhou

Recently,three groups independently identified ubiquitin-specific peptidase 21(USP21)as an efficient deubiquitylase that reverses Nanog polyubiquitylation and stabilizes Nanog *** this preview,I have summarized the wo... 详细信息

关键词： Nanog ubiquitin USP

Transitions between epithelial and mesenchymal states during cell fate conversions

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Protein & cell 2014年第8期5卷 580-591页

作者： Xiang Li Duanqing Pei Hui Zheng CAS key laboratory of regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510530 China

cell fate conversion is considered as the changing of one type of cells to another type including somatic cell reprogramming （de-differentiation）, differentiation, and trans-differentiation, Epithelial and mesenchymal cells are two major types of cells and the transitions between these two cell states as epithelial-mesenchymal transi- tion （EMT） and mesenchymal-epithelial transition （MET） have been observed during multiple cell fate conversions including embryonic development, tumor progression and somatic cell reprogramming. In addition, MET and sequential EMT-MET during the generation of induced pluripotent stem cells （iPSC） from fibroblasts have been reported recently. Such observation is consistent with multiple rounds of sequential EMT-MET during embryonic development which could be considered as a reversed process of reprogramming at least partially. Therefore in current review, we briefly discussed the potential roles played by EMT, MET, or even sequential EMT-MET during different kinds of cell fate conversions. We also provided some preliminary hypotheses on the mechanisms that connect cell state transitions and cell fate conversions based on results collected from cell cycle, epigenetic regulation, and sternness acquisition.

关键词： EMT MET cell states cell fateconversion iPSC generation trans-differentiation,differentiation

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