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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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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

The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury

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Neural regeneration research 2025年第11期20卷 3233-3244页

作者： Xiaoling Zhong Wenjiao Tai Meng-Lu Liu Shuaipeng Ma Tianjin Shen Yuhua Zou Chun-Li Zhang department of Molecular Biology University of Texas Southwestern Medical CenterDallasTXUSA Hamon center for regenerative Science and medicine University of Texas Southwestern Medical CenterDallasTXUSA Peter O’donnell Jr.Brain Institute University of Texas Southwestern Medical CenterDallasTXUSA

The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following *** targeting this pathway is beneficial to brain injury remains *** this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral *** inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology ***,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin *** findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.

关键词： adeno-associated virus Citron homology Citron homology domain gene therapy mitogen-activated protein kinase kinase kinase kinases traumatic brain injury

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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Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural regeneration research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical research center for Geriatric disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Sports medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the rNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated rNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TrIB2

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

FUBP3 mediates the amyloid-β-induced neuronal NLrP3 expression

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Neural regeneration research 2025年第7期20卷 2068-2083页

作者： Jing Yao Yuan Li Xi Liu Wenping Liang Yu Li Liyong Wu Zhe Wang Weihong Song The National Clinical research center for Geriatric disease Xuanwu HospitalCapital Medical UniversityBeijingChina department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina department of Pediatrics The Second Affiliated Hospital and Yuying Children’s HospitalKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang ProvinceChina Oujiang Laboratory(Zhejiang Laboratory for regenerative medicine Visionand Brain Health)WenzhouZhejiang ProvinceChina

Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the *** NLrP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and *** NLrP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLrP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory ***,we found that neurons also express NLrP3 in vitro and in vivo,and that neuronal NLrP3 regulates tau *** biochemical methods,we mapped the minimal NLrP3 promoter and identified FUBP3 as a transcription factor regulating NLrP3 expression in *** primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLrP3 expression and tau phosphorylation only when amyloid-βis *** the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical *** analysis suggested that FUBP3 plays a role in neuron-mediated immune *** also found that FUBP3 trimmed the 5′end of dNA fragments that it bound,implying that FUBP3 functions in stress-induced *** findings suggest that neuronal NLrP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLrP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLrP3 expression in *** that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

关键词： 5′end trimming Alzheimer's disease amyloid-beta amyloid-β-dependent transcription FUBP3 inflammasome inflammation neuron NLrP3 tau transcription factor

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

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Neural regeneration research 2025年第10期20卷 2923-2937页

作者： Yan Li Peng Hao Hongmei duan Fei Hao Wen Zhao Yudan Gao Zhaoyang Yang Kwok-Fai So Xiaoguang Li department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina China rehabilitation Science Institute China Rehabilitation Research CenterBeijing Key Laboratory of Neural Injury and RehabilitationBeijingChina center of Neural Injury and repair Beijing Institute for Brain DisordersBeijingChina Beijing Key Laboratory for Biomaterials and Neural regeneration School of Engineering MedicineBeihang UniversityBeijingChina Guangdong-HongKong-Macao Institute of CNS regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou regenerative medicine and Health Guangdong Laboratory) GuangzhouGuangdong ProvinceChina department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina center for Brain Science and Brain-Inspired Intelligence Guangdong-HongKong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina department of Biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after ***,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains *** this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic *** findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated ***,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain *** findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

关键词： adult endogenous neurogenesis basic fibroblast growth factor-hyaluronic acid collagen gel cortical remodeling functional recovery migration motor cortex injury neural circuits neural stem cells newborn neurons proliferation

C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

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Neural regeneration research 2025年第8期20卷 2231-2244页

作者： Xiangzi Wang Xiaofei Niu Yingkai Wang Yang Liu Cheng Yang Xuyi Chen Zhongquan Qi School of medicine Guangxi UniversityNanningGuangxi Zhuang Autonomous RegionChina Graduate School of Tianjin University of Traditional Chinese medicine TianjinChina Characteristic Medical center of People’s Armed Police Forces TianjinChina Fujian Maternity and Child Health Hospital FuzhouFujian ProvinceChina

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory *** expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after *** studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for *** review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord ***,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted ***,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

关键词： apoptosis C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway C-C motif chemokine receptor 2 antagonists chemokine ligand 2 chemokine receptor 2 inflammation macrophage microglia spinal cord injury therapeutic method