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Single-cell and spatial omics:exploring hypothalamic heterogeneity

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Neural Regeneration Research 2025年第6期20卷 1525-1540页

作者： Muhammad Junaid Eun Jeong Lee Su Bin Lim department of Biochemistry&Molecular Biology Ajou University School of MedicineSuwonSouth Korea department of biomedical sciences Graduate School of Ajou UniversitySuwonSouth Korea department of Brain Science Ajou University School of MedicineSuwonSouth Korea

Elucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. In this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements.

关键词： cellular diversity hypothalamus multi-omics single-cell transcriptomics spatial transcriptomics

High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi department of Brain Science Ajou University School of MedicineSuwonSouth Korea department of biomedical sciences Ajou University Graduate School of MedicineSuwonSouth Korea department of Neurology Ajou University School of MedicineSuwonSouth Korea department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

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Neural Regeneration Research 2025年第6期20卷 1776-1788页

作者： Zige Jiang Dexiang Liu Tingting Li Chengcheng Gai Danqing Xin Yijing Zhao Yan Song Yahong Cheng Tong Li Zhen Wang department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Neurosurgery Surgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关键词： apoptosis cystathionine-β-synthase nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide mitochondrion neuroplasticity oxidative stress quinolinic acid reactive oxygen species

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

PGLYRP1 protein as a novel mediator of cellular dialogue in neuroinflammation

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Neural Regeneration Research 2025年第7期20卷 1993-1994页

作者： Anup Bhusal Won-Ha Lee Kyoungho Suk department of Pharmacology School of MedicineKyungpook National UniversityDaeguRepublic of Korea BK21 Plus KNU biomedical Convergence Program Department of Biomedical ScienceSchool of MedicineKyungpook National UniversityDaeguRepublic of Korea School of Life sciences BK21 plus KNU Creative BioResearch GroupKyungpook National UniversityDaeguRepublic of Korea Brain Science and Engineering Institute Kyungpook National UniversityDaeguRepublic of Korea

Neuroinflammation has been identified as a crucial element in several neurological disorders. Glial cells play a critical role in directing neuroinflammation, both in deleterious and beneficial ways.

关键词： inflammation considerably

Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

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Neural Regeneration Research 2025年第1期20卷 130-138页

作者： Ilaria Martinelli Jessica Mandrioli Andrea Ghezzi Elisabetta Zucchi Giulia Gianferrari Cecilia Simonini Francesco Cavallieri Franco Valzania department of Neurosciences Azienda Ospedaliero Universitaria di ModenaModenaItaly Clinical and Experimental medicine Ph.D.Program University of Modena and Reggio EmiliaModenaItaly department of biomedical Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly Neurology Unit Neuromotor&Rehabilitation DepartmentAzienda USL-IRCCS di Reggio EmiliaReggio EmiliaItaly

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal *** the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of *** superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized *** numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this *** this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during *** multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

关键词： amyotrophic lateral sclerosis(ALS) autonomic extramotor genotype-phenotype multisystem involvement Parkinson’s disease sensory SOD1 superoxide dismutase 1 urinary vocal cord palsy

Brain age estimation:premise,promise,and problems

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Neural Regeneration Research 2025年第8期20卷 2313-2314页

作者： Jarrad Perron Ji Hyun Ko Graduate Program in biomedical Engineering Price Faculty of EngineeringUniversity of ManitobaWinnipegMBCanada PrairieNeuro Research Centre Kleysen Institute for Advanced MedicineHealth Sciences CentreWinnipegMBCanada department of Human Anatomy and Cell Science Rady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada

Premise:The com bined effects of modern healthcare practices which prolong lifespan and declining birthrates have created unprecedented changes in age demographics worldwide that are especially pronounced in Japan,South Korea,Europe,and North *** old age is the most significant predictor of dementia,global healthcare systems must rise to the challenge of providing care for those with neurodegenerative disorders.

关键词： estimation providing birth

A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

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Neural Regeneration Research 2025年第7期20卷 2029-2037页

作者： Xiao Liang Xingping Quan Xiaorui Geng Yujing Huang Yonghua Zhao Lei Xi Zhen Yuan Ping Wang Bin Liu Faculty of Health sciences University of MacaoMacao Special Administrative RegionChina Center for Cognitive and Brain sciences University of MacaoMacao Special Administrative RegionChina department of biomedical Engineering Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina State Key Laboratory of Quality Research in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina department of Emergency Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral ***,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly *** this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed *** observed the molding process in mice of different ages and presented age-dependent vascular embolism ***,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a *** imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

关键词： age-dependent cerebral cortex ischemic stroke mouse model optical coherence tomography angiography photoacoustic microscopy photothrombosis vascular imaging

Regulation of sleep by astrocytes in the hypothalamic ventrolateral preoptic nucleus

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Neural Regeneration Research 2025年第4期20卷 1098-1100页

作者： Jae-Hong Kim Ruqayya Afridi Il-Sung Jang Maan Gee Lee Kyoungho Suk Brain Korea 21 four KNU Convergence Educational Program of biomedical sciences for Creative Future Talents School of MedicineKyungpook National UniversityDaeguRepublic of Korea department of Pharmacology School of MedicineKyungpook National UniversityDaeguRepublic of Korea department of Pharmacology School of DentistryKyungpook National UniversityDaeguRepublic of Korea Brain Science&Engineering Institute Kyungpook National UniversityDaeguRepublic of Korea

Astrocytes are functionally dynamic cells that support neurons in multiple ways throughout an organism’s *** astrocytic regulation of neuronal activity has been increasingly recognized in recent *** are now recognized as playing a more complex role than mere bystanders in the central nervous ***,their role in regulating the sleep neurocircuitry is not well *** this perspective,we highlight the role of astrocytes in sleep modulation,with a particular focus on regulatory mechanisms related to the ventrolateral preoptic nucleus(VLPO)of the *** briefly discuss recent literature reporting the role of VLPO astrocytes in regulating sleep-associated behaviors.

关键词： sleep ventrolateral astrocytes