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Zebrafish ppp1r21 mutant as a model for the study of primary biliary cholangitis

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Journal of Genetics and Genomics 2023年第12期50卷 1004-1013页

作者： Chaoying Wu Wenfeng Zhang Yiyu Luo Chaoqing Cheng Xinjuan Wang Yan Jiang Shuang Li Lingfei Luo Yun Yang institute of developmental biology and regenerative Medicine Southwest UniversityBeibeiChongqing 400715China

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease that progresses to fibrosis and cirrhosis, resulting from the gradual destruction of intrahepatic bile ducts. Exploring genetic variants associated with PBC is essential to understand the pathogenesis of PBC. Here we identify a zebrafish balloon dog (blg) mutant with intrahepatic bile duct branching defects, exhibiting several key pathological PBC-like features, including immunodominant autoantigen PDC-E2 production, cholangiocyte apoptosis, immune cell infiltration, inflammatory activation, and liver fibrosis. blg encodes the protein phosphatase 1 regulatory subunit 21 (Ppp1r21), which is enriched in the liver and its peripheral tissues and plays a vital role in the early intrahepatic bile duct formation stage. Further studies show an excessive activation of the PI3K/AKT/mTOR pathway in the hepatic tissues in the mutant, while treatment with the pathway inhibitor LY294002 and rapamycin partially rescues intrahepatic bile duct branching defects and alleviates the PBC-like symptoms. These findings implicate the potential role of the Ppp1r21-mediated PI3K/AKT/mTOR pathway in the pathophysiology of PBC.

关键词： Zebrafish mutant ppp1r21 Primary biliary cholangitis PDC-E2 PI3K/AKT/mTOR pathway

Breaking the final barrier in reproductive animal cloning: macaque monkeys cloned

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National Science Review 2018年第3期5卷 301-303页

作者： Hongjun Song Guo-li Ming Department of Neuroscience and Mahoney institute for Neurosciences Department of Cell and Developmental Biology Institute for Regenerative Medicine University of Pennsylvania

Animal models are essential in research aiming to understand human biology and diseases,yet far too often clinical trials fail with drugs and therapeutic approaches that have been developed through,tested and built up... 详细信息

关键词： Breaking the final barrier in reproductive animal cloning macaque monkeys cloned

Intersectional gene inactivation: there is more to conditional mutagenesis than Cre

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Science China(Life Sciences) 2018年第9期61卷 1115-1117页

作者： Philippe Soriano Department of Cell Developmental and Regenerative Biology Icahn School of Medicine at Mount Sinai

The efforts of many laboratories worldwide and large scale international mutagenesis consortia have resulted in mutagenesis of nearly all mouse genes, and present efforts are devoted to large scale phenotyping of germline null mutant mice (Ayadi et al., 2012). Although early lethality associated with loss of function of a given gene may prevent elucidating its function at a later stage or in a given tissue, conditional alleles in which a critical part of the gene is flanked by recombinase target sites provide an opportunity for addressing gene function at later stages (Branda and Dymecki,2004). Fortunately, many of the mutant alleles generated by the consortia allow for conditional mutagenesis using site directed recombinases.

关键词： there is more to conditional mutagenesis than Cre

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

Oligodendroglial heterogeneity in health,disease,and recovery:deeper insights into myelin dynamics

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Neural Regeneration Research 2025年第11期20卷 3179-3192页

作者： Pieter-Jan Serneels Julie D.De Schutter Lies De Groef Lieve Moons Steven Bergmans KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionNeural Circuit Development&Regeneration Research GroupLeuvenBelgium KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionCellular Communication&Neurodegeneration Research GroupLeuvenBelgium

Decades of research asserted that the oligodendroglial lineage comprises two cell types:oligodendrocyte precursor cells and ***,recent studies employing single-cell RNA sequencing techniques have uncovered novel cell states,prompting a revision of the existing *** forward,the oligodendroglial lineage should be delineated into five distinct cell states:oligodendrocyte precursor cells,committed oligodendrocyte precursor cells,newly formed oligodendrocytes,myelin-forming oligodendrocytes,and mature *** new classification system enables a deeper understanding of the oligodendroglia in both physiological and pathological *** this uniform terminology will facilitate comparison and integration of data across ***,including the consolidation of findings from various demyelinating models,is essential to better understand the pathogenesis of demyelinating ***,comparing injury models across species with varying regenerative capacities can provide insights that may lead to new therapeutic strategies to overcome remyelination ***,by standardizing terminology and synthesizing data from diverse studies across different animal models,we can enhance our understanding of myelin pathology in central nervous system disorders such as multiple sclerosis,Alzheimer's disease,and amyotrophic lateral sclerosis,all of which involve oligodendroglial and myelin dysfunction.

关键词： animal models demyelination fish mammals multiple sclerosis myelin neurodegeneration oligodendrocytes oligodendroglial lineage remyelination

ImSpiRE: image feature-aided spatial resolution enhancement method

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Science China Life Sciences 2025年第1期 272-283页

作者： Yuwei Hua Yizhi Zhang Zhenming Guo Shan Bian Yong Zhang State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center Institute for Regenerative MedicineDepartment of NeurosurgeryShanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji University

The resolution of most spatially resolved transcriptomic technologies usually cannot attain the single-cell level, limiting their applications in biological discoveries. Here, we introduce ImSpiRE, an image feature-aided spatial resolution enhancement method for in situ capturing spatial transcriptome. Taking the information stored in histological images, ImSpiRE solves an optimal transport problem to redistribute the expression profiles of spots to construct new transcriptional profiles with enhanced resolution, together with extending the gene expression profiles into unmeasured regions. Applications to multiple datasets confirm that ImSpiRE can enhance spatial resolution to the subspot level while contributing to the discovery of tissue domains, signaling communication patterns, and spatiotemporal characterization.

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Neuropeptide cholecystokinin:a key neuromodulator for hippocampal functions

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Neural Regeneration Research 2025年第7期20卷 1991-1992页

作者： Fengwen Huang Stephen Temitayo Bello Department of Neuroscience City University of Hong KongKowloon TongHong Kong Special Administrative RegionChina Center for regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong Special Administrative RegionChina

Spatial memory is crucial for survival within external surroundings and wild *** hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and *** neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal ***(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target *** instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety ***,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.

关键词： abundant functions modulator

Immunomodulative effects of mesenchymal stem cells derived from human embryonic stem cells in vivo and in vitro

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第1期12卷 18-27页

作者： Zhou TAN Zhong-yuan SU Rong-rong WU Bin GU Yu-kan LIU Xiao-li ZHAO Ming ZHANG institute of Cell biology and Genetics College of Life Sciences Zhejiang University Hangzhou 310058 China institute of developmental and regenerative biology College of Life and Environmental Sciences Hangzhou Normal University Hangzhou 310036 China

Objective: Human embryonic stem cells (hESCs) have recently been reported as an unlimited source of mesenchymal stem cells (MSCs).The present study not only provides an identical and clinically compliant MSC source derived from hESCs (hESC-MSCs),but also describes the immunomodulative effects of hESC-MSCs in vitro and in vivo for a carbon tetrachloride (CCl4)-induced liver inflammation ***: Undifferentiated hESCs were treated with Rho-associated kinase (ROCK) inhibitor and induced to fibroblast-looking *** cells were tested for their surface markers and multilineage differentiation *** more,we analyzed their immune characteristics by mixed lymphocyte reactions (MLRs) and animal ***: hESC-MSCs show a homogenous fibroblastic morphology that resembles bone marrow-derived MSCs (BM-MSCs).The cell markers and differentiation potential of hESC-MSCs are also similar to those of *** their original cells,hESC-MSCs possess poor immunogenicity and can survive and be engrafted into a xenogenic immunocompetent ***: The hESC-MSCs demonstrate strong inhibitory effects on lymphocyte proliferation in vitro and anti-inflammatory infiltration properties in *** study offers information essential to the applications of hESC-MSC-based therapies and evidence for the therapeutic mechanisms of action.

关键词： Human embryonic stem cells Mesenchymal stem cells Differentiation Immunomodulative effects

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