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Epigenetic control on cell fate choice in neural stem cells

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Protein & Cell 2012年第4期3卷 278-290页

作者： Xiao-Ling Hu Yuping Wang Qin Shen Center for Stem Cell biology and regenerative Medicine School of MedicineTsinghua Center for Life SciencesTsinghua UniversityBeijing 100084China department of Pharmacy Tianjin Children’s HospitalTianjin 300074China

Derived from neural stem cells(NSCs)and progenitor cells originated from the neuroectoderm,the nervous system presents an unprecedented degree of cellular diversity,interwoven to ensure correct connections for propagating information and responding to environ-mental *** and progenitor cells must integrate cell-intrinsic programs and environmental cues to achieve production of appropriate types of neurons and glia at appropriate times and places during *** developmental dynamics are reflected in changes in gene expression,which is regulated by transcription factors and at the epigenetic *** early commitment of neural lineage to functional plas-ticity in terminal differentiated neurons,epigenetic regulation is involved in every step of neural *** we focus on the recent advance in our un-derstanding of epigenetic regulation on orderly genera-tion of diverse neural cell types in the mammalian nervous system,an important aspect of neural devel-opment and regenerative medicine.

关键词： neural stem cells(NSCs) epigenetic regu-lation neurogenesis gliogenesis radial glial cell cerebral cortex subventricular zone(SVZ) DNA methylation histone modification

Does mesenchymal stem cell’s secretome affect spinal sensory circuits?Implication for pain therapies

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Neural Regeneration Research 2025年第1期20卷 181-183页

作者： Francesco Ferrini Esri H.Juárez Adalberto Merighi department of Veterinary Sciences University of TurinGrugliascoTOItaly department of Psychiatry and Neuroscience UniversitéLavalQuébec CityQCCanada

Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical *** have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue *** enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC *** increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.

关键词： protective clinical collective

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

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

AIAP: A Quality Control and Integrative Analysis Package to Improve ATAC-seq Data Analysis

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Genomics, Proteomics & Bioinformatics 2021年第4期19卷 641-651页

作者： Shaopeng Liu Daofeng Li Cheng Lyu Paul MGontarz Benpeng Miao Pamela A.F.Madden Ting Wang Bo Zhang department of Developmental biology Center of Regenerative MedicineWashington University School of MedicineSt.LouisMO 63108USA department of Genetics Center for Genomic Sciences and Systems BiologyWashington University School of MedicineSt.LouisMO 63108USA department of Psychiatry Washington University School of MedicineSt.LouisMO 63108USA

Assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq) is a technique widely used to investigate genome-wide chromatin accessibility. The recently published Omni-ATAC-seq protocol substantially improves the signal/noise ratio and reduces the input cell number. High-quality data are critical to ensure accurate *** tools have been developed for assessing sequencing quality and insertion size distribution for ATAC-seq data;however, key quality control(QC) metrics have not yet been established to accurately determine the quality of ATAC-seq data. Here, we optimized the analysis strategy for ATAC-seq and defined a series of QC metrics for ATAC-seq data,including reads under peak ratio(RUPr), background(BG), promoter enrichment(Pro En), subsampling enrichment(Sub En), and other measurements. We incorporated these QC tests into our recently developed ATAC-seq Integrative Analysis Package(AIAP) to provide a complete ATAC-seq analysis system, including quality assurance, improved peak calling, and downstream differential analysis. We demonstrated a significant improvement of sensitivity(20%–60%) in both peak calling and differential analysis by processing paired-end ATAC-seq datasets using AIAP. AIAP is compiled into Docker/Singularity, and it can be executed by one command line to generate a comprehensive QC report. We used ENCODE ATAC-seq data to benchmark and generate QC recommendations, and developed q ATACViewer for the userfriendly interaction with the QC report. The software, source code, and documentation of AIAP are freely available at https://***/Zhang-lab/ATAC-seq_QC_analysis.

关键词： ATAC-seq Quality control Chromatin accessibility Differential analysis Data visualization

Oligodendrocyte ablation as a tool to study demyelinating diseases

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Neural Regeneration Research 2016年第6期11卷 886-889页

作者： Ahdeah Pajoohesh-Ganji Robert H.Miller department of Anatomy and regenerative biology The George Washington University School of Medicine and Health Sciences

Multiple sclerosis（MS） is an autoimmune mediated neurodegenerative disease characterized by demyelination and oligodendrocyte（OL） loss in the central nervous system and accompanied by local inflammation and infiltration of peripheral immune cells. Although many risk factors and symptoms have been identified in MS, the pathology is complicated and the cause remains unknown. It is also unclear whether OL apoptosis precedes the inflammation or whether the local inflammation is the cause of OL death and demyelination. This review briefly discusses several models that have been developed to specifically ablate oligodendrocytes in an effort to separate the effects of demyelination from inflammation.

关键词： inflammation autoimmune ablation unclear infiltration accompanied briefly myelin impairment neuronal

RNAi screen in Drosophila yields a fat catch of Hedgehog

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Protein & Cell 2010年第3期1卷 205-206页

作者： Steven Y Cheng Center for regenerative Medicine and department of Developmental Genetics Nanjing Medical UniversityNanjing 210029China

Obesity,the scrooge of technological advances of the human society,just had its genetic makings revealed once again.A large international team led by Josef *** and Harald Esterbauer from the Austrian Academy of Sciences and Medical University of Vienna have conducted a systemic hunt for obesity genes in adult Drosophila using an ingenious design of RNAi-based screening strategy(Pospisilik et al.,2010).This study covered 78%of Drosophila genome,including 30%of genes that would otherwise cause embryonic lethality if inactivated by conventional *** findings included~500 obesity genes that have their functions linked to control of differentiation along neuronal,muscle,and oenocyte lineages,but components of the Hedgehog(Hh)signaling distinguished themselves as the top-scoring hits。

关键词： Hedgehog otherwise finding

Neuronal reprogramming in treating spinal cord injury

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Neural Regeneration Research 2022年第7期17卷 1440-1445页

作者： Xuanyu Chen Hedong Li department of Neuroscience&regenerative Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Spinal cord injury represents a devastating central nervous system injury that could impair the mobility and sensory function of afflicted *** hallmarks of spinal cord injury include neuroinflammation,axonal degeneration,neuronal loss,and reactive ***,the formation of a glial scar at the injury site elicits an inhibitory environment for potential *** axonal regeneration,a significant challenge in treating spinal cord injury is to replenish the neurons lost during the pathological ***,despite decades of research efforts,current strategies including stem cell transplantation have not resulted in a successful clinical ***,stem cell transplantation faces serious hurdles such as immunorejection of the transplanted cells and ethical *** vivo neuronal reprogramming is a recently developed technology and leading a major breakthrough in regenerative *** innovative technology converts endogenous glial cells into functional neurons for injury repair in the central nervous *** feasibility of in vivo neuronal reprogramming has been demonstrated successfully in models of different neurological disorders including spinal cord injury by numerous *** reprogramming factors,mainly the pro-neural transcription factors,have been utilized to reprogram endogenous glial cells into functional neurons with distinct *** far,the literature on in vivo neuronal reprogramming in the model of spinal cord injury is still *** this review,we summarize a limited number of such reports and discuss several questions that we think are important for applying in vivo neuronal reprogramming in the research field of spinal cord injury as well as other central nervous system disorders.

关键词： astrocyte microRNA NeuroD1 neuronal relay neuronal reprogramming NG2 glia pericyte reactive gliosis Sox2 spinal cord injury

Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma

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World Journal of Gastroenterology 2016年第1期22卷 275-283页

作者： Yukihiro Haruyama Hiroaki Kataoka Section of Oncopathology and regenerative biology Department of PathologyFaculty of MedicineUniversity of Miyazaki

Glypican-3(GPC3)is a cell surface oncofetal proteoglycan that is anchored by *** GPC3 is abundant in fetal liver,its expression is hardly detectable in adult ***,GPC3is overexpressed in hepatocellular carcinoma(HCC),and several immunohistochemical studies reported that overexpression predicts a poorer prognosis for HCC ***,GPC3 would serve as a useful molecular marker for HCC diagnosis and also as a target for therapeutic intervention in ***,some immunotherapy protocols targeting GPC3 are under investigations;those include humanized anti-GPC3cytotoxic antibody,peptide vaccine and immunotoxin *** considering the clinical requirements for GPC3-targeting therapy,companion diagnostics to select the appropriate HCC patients are critical,and both immunohistochemical analysis of tissue sections and measurement of serum GPC3 level have been suggested for this *** review summarizes current knowledge regarding the clinical implication of GPC3detection and targeting in the management of patients with HCC.

关键词： Glypican-3 Enzyme-linked immunosorbentassay Hepatocellular carcinoma Prognosis Companiondiagnostics Immunohistochemistry