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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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Computational protein design and structure prediction—the 2024Nobel prize in chemistry

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Science China Chemistry 2025年

作者： Peilong Lu Lei Liu School of life sciences and Research center for Industries of the Future Westlake University tsinghua-peking Joint center for life sciences Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology Center for Synthetic and Systems Biology Department of Chemistry Tsinghua University

The 2024 Nobel prize in chemistry recognizes groundbreaking advancements in protein science, highlighting the power of artificial intelligence (AI) to decipher and design the molecular machinery of life. Half of the prize was awarded to David Baker for the computational design of proteins; the other to Demis Hassabis and John Jumper for their AI-driven predictions of protein structures. This article briefly reviews their achievements, and discusses the opportunities and directions that their work has enabled (Figure1).

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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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Quantum convolution inequalities on Frobenius von Neumann algebras

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Science China Mathematics 2025年

作者： Linzhe Huang Zhengwei Liu Jinsong Wu Beijing Institute of Mathematical sciences and Applications Yau Mathematical sciences center and Department of Mathematics Tsinghua University

In this paper, we introduce Frobenius von Neumann algebras and study quantum convolution inequalities. In this framework, we unify quantum Young's inequality on quantum symmetries such as subfactors,and fusion bi-algebras studied in quantum Fourier analysis. Moreover, we prove quantum entropic convolution inequalities and characterize the extremizers in the subfactor case. We also prove quantum smooth entropic convolution inequalities. We obtain the positivity of comultiplications of subfactor planar algebras, which is stronger than the quantum Schur product theorem. All these inequalities provide analytic obstructions of unitary categorification of fusion rings stronger than the Schur product criterion.

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Revealing and predicting the long-term biomechanical response of orthokeratology by developing a patient-specific computational model

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 156-168页

作者： Yifeng Li Zhuoran Yang Ziming Yan Huibin Shi Zhanli Liu Kaijie Wang Department of Engineering Mechanics School of Aerospace Engineering Tsinghua University Beijing Tongren Eye center Beijing Tongren Hospital Capital Medical University Beijing Ophthalmology & Visual Sciences Key Lab

Orthokeratology(OK) is widely used for effective myopia correction and control. However, the incomplete understanding of its biomechanical mechanisms makes OK lens fitting rely heavily on clinician judgment, complicating accurate predictions of treatment outcomes. In this paper, we performed clinical experiments and numerical analysis to study corneal deformation modes and long-term changes in central corneal thickness. Clinical experiments were conducted on 194 Chinese myopic patients under OK treatment for 3 months. Based on the experimental data, a patient-specific computational biomechanical model for OK was established and validated. Specifically, the anisotropic mechanical properties of the cornea were incorporated into the model to describe the significant difference between its shear modulus(29.5 kPa) and tensile modulus(768.4 kPa). Additionally, a viscohyperelastic material model with a prolonged corneal relaxation time of 5.6 h was developed to capture the long-term deformation response. The results show that corneal thickness reduction in OK is primarily due to out-of-plane shear deformation,influenced by the cornea's low shear resistance. Modeling the extended corneal relaxation time is crucial for predicting long-term biomechanical responses. The computational model effectively captures long-term changes in central corneal thickness, potentially improving OK lens fitting accuracy.

关键词： orthokeratology computational biomechanical model long-term viscoelasticity myopia correction

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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of life sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina Institute of Basic Medical sciences Chinese Academy of Medical sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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Mechanism by which Rab5 promotes regeneration and functional recovery of zebrafish Mauthner axons

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Neural Regeneration Research 2025年第6期20卷 1816-1824页

作者： Jiantao Cui Yueru Shen Zheng Song Dinggang Fan Bing Hu center for Advanced Interdisciplinary Science and Biomedicine of IHM Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina

Rab5 is a GTPase protein that is involved in intracellular membrane trafficking. It functions by binding to various effector proteins and regulating cellular responses, including the formation of transport vesicles and their fusion with the cellular membrane. Rab5 has been reported to play an important role in the development of the zebrafish embryo;however, its role in axonal regeneration in the central nervous system remains unclear. In this study, we established a zebrafish Mauthner cell model of axonal injury using single-cell electroporation and two-photon axotomy techniques. We found that overexpression of Rab5 in single Mauthner cells promoted marked axonal regeneration and increased the number of intra-axonal transport vesicles. In contrast, treatment of zebrafish larvae with the Rab kinase inhibitor CID-1067700markedly inhibited axonal regeneration in Mauthner cells. We also found that Rab5 activated phosphatidylinositol 3-kinase(PI3K) during axonal repair of Mauthner cells and promoted the recovery of zebrafish locomotor function. Additionally, rapamycin, an inhibitor of the mechanistic target of rapamycin downstream of PI3K, markedly hindered axonal regeneration. These findings suggest that Rab5 promotes the axonal regeneration of injured zebrafish Mauthner cells by activating the PI3K signaling pathway.

关键词： axonal regeneration Mauthner cell nerve regeneration Rab5 zebrafish

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Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis

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Science China life sciences 2025年

作者： Chuan Ye Xuemei Wang Jun Lin Chenyang Wu Yuhua Gao Chenghao Guo Yunxi Liao Ziyan Rao Shaodong Huang Weixuan Chen Ying Huang Jinpeng Sun Dongyu Zhao Changtao Jiang center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third Hospital Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University Department of Biomedical Informatics School of Basic Medical SciencesPeking University State Key Laboratory of Vascular Homeostasis and Remodeling Peking University center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking University State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyPeking University Third Hospital National Clinical Research center for Obstetrics and Gynecology Peking University Third Hospital Department of Endocrinology and Metabolism Peking University Third Hospital Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong University Department of Immunology School of Basic Medical SciencesPeking University

Adipogenesis is the healthy expansion of white adipose tissue (WAT),serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the ***,the identification of novel regulatory molecules in adipogenesis,specifically membrane receptors such as G protein-coupled receptors (GPCRs),holds significant clinical *** receptors can serve as viable targets for pharmaceuticals,offering potential for restoring metabolic homeostasis in individuals with *** utilized trajectory inference methods to analyze three distinct single-nucleus sequencing (sNuc-seq) datasets of adipose tissue and systematically identified GPCRs with the potential to regulate *** verification in primary adipose progenitor cells (APCs) of mice,we discovered that ADGRD1 promoted the differentiation of APCs,while GPR39 inhibits this *** the obese mouse model induced by a high-fat diet(HFD),both gain-of-function and loss-of-function studies validated that ADGRD1 promoted adipogenesis,thereby improving metabolic homeostasis,while GPR39 inhibited adipogenesis,leading to metabolic ***,through the analysis of 2,400 ChIP-seq data and 1,204 bulk RNA-seq data,we found that the transcription factors (TFs) MEF2D and TCF12 regulated the expression of ADGRD1and GPR39,*** study revealed the regulatory role of GPCRs in adipogenesis,providing novel targets for clinical intervention of metabolic dysfunction in obese patients.

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Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

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Science China life sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng Huang Zhijun Wu Baitao Liu Hongjie Huang Haijun Wang Yongjian Wang Dingge Liu Zhihua Zhang Kaiping Liu Gang Yang Xi Gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe Laboratory of Cell Ecosystem Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of Cardiovascular sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key Laboratory of Sports Injuries Engineering Research center of Sports Trauma Treatment Technology and Devices Ministry of Education State Key Laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University peking University Health Science Centre Peking University Department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

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Neural Regeneration Research 2025年第1期20卷 209-223页

作者： Shi-Yan Sun Lingyun Nie Jing Zhang Xue Fang Hongmei Luo Chuanhai Fu Zhiyi Wei Ai-Hui Tang Hefei National Research center for Physical sciences at the Microscale CAS Key Laboratory of Brain Function and DiseaseMinistry of Education Key Laboratory for Membrane-less Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina CAS center for Excellence in Molecular Cell sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurobiology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Brain Research center Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and ***-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains *** this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative ***,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic *** of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and *** down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive *** together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

关键词： actin cytoskeleton dendrite KANK1 KIF21A microtubule spine morphology spine synaptic plasticity talin1

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