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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National clinical research center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina shanghai Engineering research center of Stem Cells translational Medicine ShanghaiChina National center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain research BeijingChina research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering research center of Digital Healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Altered 3D genome reorganization mediates precocious myeloid differentiation of aged hematopoietic stem cells in inflammation

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Science China Life Sciences 2025年

作者： Xinyu Cui Yu Dong Qiang Zhan Yixin Huang Qianshu Zhu Zihao Zhang Guang Yang Liping Wang Shijun Shen Jia Zhao Zhiyi Lin Jiatong Sun Zhongqu Su Yihan Xiao Chuyu Zhang Yuwei Liang Lu Shen Lichen Ji Xuguang Zhang Jiqing Yin Hong Wang Zhiyang Chen Zhenyu Ju Cizhong Jiang Rongrong Le Shaorong Gao clinical and translational research center of shanghai first maternity & infant hospital Frontier Science Center for Stem Cells School of Life Sciences and Technology Tongji University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji Hospital School of Life Sciences and Technology Tongji University Key Laboratory of Regenerative Medicine of Ministry of Education Institute of Aging and Regenerative Medicine Department of Developmental & Regenerative Medicine College of Life Science and Technology Jinan University Shandong Key Laboratory of Animal Bioengineering and Disease Prevention College of Animal Science and Technology Shandong Agricultural University Department of Joint Surgery Shanghai East Hospital Tongji University School of Medicine shanghai Institute of Nutrition and Health Chinese Academy of Sciences

Inflammation is a driving force of hematopoietic stem cells(HSCs) aging, causing irreversible exhaustion of functional HSCs. However, the underlying mechanism of HSCs erosion by inflammatory insult remains poorly understood. Here, we find that transient LPS exposure primes aged HSCs to undergo accelerated differentiation at the expense of self-renewal, leading to depletion of HSCs. Meanwhile, the central regulator nuclear factor kappa B(NF-κB) mediating functional impairment by inflammation insult induces differential transcriptional response in aged HSCs compared with young HSCs, with precocious activation of myeloid lineage genes. Altered compartmentalization and chromatin loop formation are associated with aging-related differential transcriptional response in HSCs upon lipopolysaccharide(LPS)stimulation. Mechanistically, enhancer and promoter regions of myeloid lineage genes in aged HSCs are more accessible and display more rapid and prominent CTCF occupancy upon LPS stimulation. Our study provides comprehensive resources for the three-dimensional(3D)genome structure of HSCs and sheds light into the ordered genome organization and the associated transcriptome signature underlying HSCs aging.

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of translational research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Department of clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteractionclinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration research 2025年第7期20卷 1849-1863页

作者： Xiaodong Xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing Xu Yan Liu Jian Zhang Department of clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina College of Pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes

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Cloning non-HUMAN primates by somatic cell nuclear transfer

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Science China(Life Sciences) 2018年第3期61卷 361-362页

作者： Shaorong Gao clinical and translational research center of shanghai first maternity and infant hospital School of Life Sciences and Technology Tongji University

The recent breakthrough in successful producing cloned non- human primates by somatic cell nuclear transfer （SCNT） has attracted great attention both scientifically and publically （Liu et al., 2018）. Two macaque monkeys, named ＂Zhongzhong＂ and ＂Huahua＂, were cloned from fetal fi- broblast cells by Chinese scientists using the technique that produced the first cloned mammal ＂Dolly＂ 21 years ago （Wilmut et al., 1997）. The first cloned sheep has re- volutionized our thinking that the mammalian somatic cells can be reprogrammed into totipotent embryos by SCNT, although the efficiency is extremely low. Actually, in the same year when ＂Dolly＂ was reported, a paper published in Biology of Reproduction also attracted broad attention in which two rhesus monkeys were produced from blastomeres isolated from 4-cell stage embryos using the same technique （Meng et al., 1997）. However, it remains very challenging if the somatic cells from monkeys can be reprogrammed into totipotent embryos, although many laboratories all over the world have tried very hard in the past 20 years. Indeed, the successful cloning of monkeys today is attributed to both the technical improvement and the progress obtained in me- chanistic studies in reprogramming. Two major techniques are involved in SCNT. The first is called enucleation through which the spindle-chromosome complex （SCC） of an oocyte at metaphase II （MII） stage is removed by an enucleation pipette. The enucleation process is relatively easy for mouse oocytes since the SCC can be visualized under light micro- scope, but the SCC of oocytes from large animals including

关键词：原子转移克隆房间技术改进人类卵母细胞哺乳动物 SCC

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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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Lessons from expanded potential of embryonic stem cells:Moving toward totipotency

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Journal of Genetics and Genomics 2020年第3期47卷 123-130页

作者： Rongrong Le Yixin Huang Anqi Zhao Shaorong Gao clinical and translational research center of shanghai first maternity&infant hospital Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai200092China

Embryonic stem cells possess fascinating capacity of self-renewal and developmental potential,leading to significant progress in understanding the molecular basis of pluripotency,disease modeling,and reprogramming ***,2-cell-like embryonic stem cells(ESCs)and expanded potential stem cells or extended pluripotent stem cells(EPSCs)generated from early-cleavage embryos display some features of totipotent *** cell lines provide valuable in vitro models to study underlying principles of totipotency,cell plasticity,and lineage *** this review,we summarize the current progress in this filed and highlight the application potentials of these cells in the future.

关键词： 2C-like ESC EPSC MERVL Zscan4 Totipotency

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LincRNA1230 inhibits the differentiation of mouse ES cells towards neural progenitors

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Science China(Life Sciences) 2016年第5期59卷 443-454页

作者： Chenxin Wang Guoping Li Yukang Wu Jiajie Xi Jiuhong Kang clinical and translational research center of shanghai first maternity and Infant Health Hospital Shanghai Key Laboratory of Signaling and Disease Research Collaborative Innovation Center for Brain Science School of Life Science and Technology Tongji University Shanghai 200092 China

In vitro, mouse embryonic stem （ES） cells can differentiate into many somatic cell types, including neurons and glial cells. When cultured in serum-free medium, ES cells convert spontaneously and efficiently to a neural fate. Previous studies have shown that the neural conversion of mouse ES cells includes both the participation of neural-specific transcription factors and the regulation of epigenetic modifications. However, the intracellular mechanism underlying this intrinsic transition still re- mains to be further elucidated. Herein, we describe a long intergenic non-coding RNA, LincRNA1230, which participates in the regulation of the neural lineage specification of mouse ES cells. The ectopic forced expression of LincRNAI230 dramatically inhibited mouse ES cells from adopting a neural cell fate, while LincRNA1230 knockdown promoted the conversion of mouse ES cells towards neural progenitors. Mechanistic studies have shown that LincRNA1230 inhibits the activation of early neural genes, such as Pax6 and Soxl, through the modulation of bivalent modifications （tri-methylation of histone3 lysine4 and his- tone3 lysine27） at the promoters of these genes. The interaction of LincRNA1230 with Wdr5 blocked the localization of Wdr5 at the promoters of early neural genes, thereby inhibiting the enrichment of H3K4me3 modifications at these loci. Collectively, these findings revealed a crucial role for LincRNA1230 in the regulation of the neural differentiation of mouse ES cells.

关键词： mouse ES cells neural differentiation long non-coding RNA (IncRNA) bivalent modification Wdr5

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Progress in understanding epigenetic remodeling during induced pluripotency

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Science Bulletin 2015年第20期60卷 1713-1721页

作者： Rui Gao Xiaoyu Liu Shaorong Gao clinical and translational research center of shanghai first maternity and infant hospital School of Life Sciences and Technology Tongji University School of Life Sciences Tsinghua University National Institute of Biological Sciences

Over 50 years of efforts, cellular reprogram- ruing opens a new door for disease modeling and regen- erative medicine. Although induction of pluripotency by transcription factors has become common, only a small portion of basic mechanisms of epigenetic modifications during this process have been revealed. To clearly under- stand reprogramming and devise ways to promote full transition towards pluripotency, we must gain insight from comprehensive characterizations of cells at distinct repro- gramming stages, which involves gene expression profil- ing, chromatin state maps of key activating and repressive marks, and DNA modifications. Here, we review recent advances in epigenetic reprogramming to pluripotency with a focus on the principal molecular regulators and attach importance to the combination of high-throughput sequencing and systematic biology approaches in uncov- ering underlying molecular mechanisms of this unique platform in future researches.

关键词： Induced pluripotency Epigeneticreprogramming Histone modifications DNA modifications

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p190A inactivating mutations cause aberrant RhoA activation and promote malignant transformation via the Hippo-YAP pathway in endometrial cancer

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1792-1803页

作者： Xiaoli Wen Jing Wan Qizhi He Mengfei Wang Shuangdi Li Mei Jiang Zhen Qian Binya Liu Wen Lu Kai Wang Kun Gao Xiaoping Wan Department of Gynecology Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghai 201204China Department of Gynecology International Peace Maternity and Child Health HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Department of Pathology Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghai 201204China Tongji University School of Medicine Shanghai 200092China clinical and translational research center Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghai 201204China

The Rho family of GTPases is strictly regulated by a large family of GTPase-activating proteins(GAPs)that stimulate the relatively weak intrinsic GTP-hydrolyzing activity of Rho GTPases.p190A is a potent and widely expressed GAP that acts on RhoA GTPases.p190A is frequently mutated in endometrial cancer,but the contribution of p190A mutations to endometrial tumorigenesis remains *** we identified that p190A is an upstream regulator of the Hippo-YAP signaling pathway,which is a critical regulator of cell proliferation,apoptosis,and cell fate.p190A knockout in endometrial cancer cells promoted cell proliferation,migration,and epithelial–mesenchymal transition(EMT),which were partially dependent on YAP ***-type p190A,but not endometrial cancer-associated mutants,suppressed the nuclear localization,transcriptional activity,and malignant transformation function of ***,the nuclear localization of YAP was enhanced in p190A-mutated endometrial *** findings reveal novel molecular mechanisms underlying Hippo-YAP pathway-driven endometrial tumorigenesis and elucidate the potential for therapy targeting the Hippo-YAP pathway in p190A-mutated endometrial cancer.

关键词： endometrial malignant cancer

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