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Functions of nuclear factor Y in nervous system development,function and health

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Neural Regeneration Research 2025年第10期20卷 2887-2894页

作者： Pedro Moreira Roger Pocock Development and Stem Cells program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVICAustralia

Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and *** the last 30 years,research has revealed that the nuclear factor Y complex controls many aspects of brain development,including differentiation,axon guidance,homeostasis,disease,and most recently ***,a complete understanding of transcriptional regulatory networks,including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains *** this review,we explore the nuclear factor Y complex’s role and mode of action during brain development,as well as how genomic technologies may expand understanding of this key regulator of gene expression.

关键词： axon guidance CCAAT boxes neuronal degeneration neuronal differentiation neuronal regeneration nuclear factor Y complex transcription factor transcriptional regulation

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

A lead role for a“secondary”axonal injury response

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Neural Regeneration Research 2025年第2期20卷 469-470页

作者： Melissa A.Rudy Trent A.Watkins Division of Neuroimmunology and Glial biology Department of NeurologyUniversity of California at San FranciscoSan FranciscoCAUSA Development Disease Modelsand Therapeutics Graduate ProgramBaylor College of MedicineHoustonTXUSA

Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system ***,this stress response drives neuronal apoptosis in non-regenerative *** duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative *** dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve *** this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).

关键词： injury axonal stress

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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Neural Regeneration Research 2025年第2期20卷 343-353页

作者： Ana Milena Silva Olaya Fernanda Martins Almeida Ana Maria Blanco Martinez Suelen Adriani Marques PhD program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate program in Pathological Anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy

VASC: Dimension Reduction and Visualization of Single-cell RNA-seq Data by Deep Variational Autoencoder

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Genomics, Proteomics & bioinformatics 2018年第5期16卷 320-331页

作者： Dongfang Wang Jin Gu MOE Key Laboratory of bioinformatics BNRIST Bioinformatics Division & Center for Synthetic and Systems BiologyDepartment of Automation Tsinghua University

Single-cell RNA sequencing(scRNA-seq) is a powerful technique to analyze the transcriptomic heterogeneities at the single cell level. It is an important step for studying cell subpopulations and lineages, with an effective low-dimensional representation and visualization of the original scRNA-Seq data. At the single cell level, the transcriptional fluctuations are much larger than the average of a cell population, and the low amount of RNA transcripts will increase the rate of technical dropout events. Therefore, scRNA-seq data are much noisier than traditional bulk RNA-seq data. In this study, we proposed the deep variational autoencoder for scRNA-seq data(VASC), a deep multi-layer generative model, for the unsupervised dimension reduction and visualization of scRNA-seq data. VASC can explicitly model the dropout events and find the nonlinear hierarchical feature representations of the original data. Tested on over 20 datasets, VASC shows superior performances in most cases and exhibits broader dataset compatibility compared to four state-of-the-art dimension reduction and visualization methods. In addition, VASC provides better representations for very rare cell populations in the 2D visualization. As a case study, VASC successfully re-establishes the cell dynamics in pre-implantation embryos and identifies several candidate marker genes associated with early embryo development. Moreover, VASC also performs well on a 10× Genomics dataset with more cells and higher dropout rate.

关键词： Single cell RNA sequencing Deep variational autoencoder Dimension reduction Visualization Dropout

A multilevel pan-cancer map links gene mutations to cancer hallmarks

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Chinese Journal of Cancer 2015年第10期34卷 439-449页

作者： Theo A.Knijnenburg Tycho Bismeijer Lodewyk F.A.Wessels llya Shmulevich Institute for systems biology bioinformatics and Statistics Division of Molecular CarcinogenesisNetherlands Cancer Institute

Background:A central challenge in cancer research is to create models that bridge the gap between the molecular level on which interventions can be designed and the cellular and tissue levels on which the disease phenotypes are *** study was undertaken to construct such a model from functional annotations and explore its use when integrated with large-scale cancer genomics ***:We created a map that connects genes to cancer hallmarks via signaling *** projected gene mutation and focal copy number data from various cancer types onto this *** performed statistical analyses to uncover mutually exclusive and co-occurring oncogenic aberrations within this ***:Our analysis showed that although the genetic fingerprint of tumor types could be very different,there were less variations at the level of hallmarks,consistent with the idea that different genetic alterations have similar functional ***,we showed how the multilevel map could help to clarify the role of infrequently mutated genes,and we demonstrated that mutually exclusive gene mutations were more prevalent in pathways,whereas many co-occurring gene mutations were associated with hallmark ***:Overlaying this map with gene mutation and focal copy number data from various cancer types makes it possible to investigate the similarities and differences between tumor samples systematically at the levels of not only genes but also pathways and hallmarks.

关键词： Cancer systems biology, Cancer hallmarks, Gene mutations, Multilevel model

Cancer bioinformatics:detection of chromatin states, SNP-containing motifs, and functional enrichment modules

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Chinese Journal of Cancer 2013年第4期32卷 153-154页

作者： Xiaobo Zhou Center for bioinformatics and systems biology Wake Forest University-School of Medicine

In this editorial preface, I briefly r eview cancer bioinformatics and introduce the four articles in this special issue highlighting important applications of the field: detection of chromatin states; detection of SNP- containing motifs and association with transcription factor-binding sites; improvements in functional enrichment modules; and gene association studies on aging and cancer. We expect this issue to provide bioinformatics scientists, cancer biologists, and clinical doctors with a better understanding of how cancer bioinformatics can be used to identify candidate biomarkers and targets and to conduct functional analysis.

关键词： Chromatin sates, SNP-containing motifs, functional enrichment analysis, gene association

Arabidopsis co-chaperonin CPN20 antagonizes Mg-chelatase H subunit to derepress ABA-responsive WRKY40 transcription repressor

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Science China(Life Sciences) 2014年第1期57卷 11-21页

作者： ZHANG XiaoFeng JIANG Tao YU YongTao WU Zhen JIANG ShangChuan LU Kai FENG XiuJing LIANG Shan LU YanFen WANG XiaoFang ZHANG DaPeng MOE systems biology and bioinformatics Laboratory School of Life Sciences Tsinghua University

Our previous study demonstrated that a chloroplast co-chaperonin 20(CPN20),one of the interaction partners of the magnesium-protoporphyrin IX chelatase H subunit(CHLH/ABAR),negatively regulates ABA signaling at the same node with ABAR but upstream of WRKY40 transcription repressor in Arabidopsis *** the present experiment,we showed that ABA directly inhibits the ABAR-CPN20 interaction,and also represses expression of CPN20,which depends on ***20 inhibits ABAR-WRKY40 interaction by competitively binding to *** downregulates,but CPN20 upregulates,WRKY40 *** cpn20-1 mutation induces downregulation of WRKY40,and suppresses the upregulated level of WRKY40 due to the cch mutation in the ABAR ***-induced repressive effect of the WRKY40 gene is strengthened by downregulation of CPN20 but reduced by upregulation of *** with our previously reported genetic data,we provide evidence that CPN20 functions through antagonizing the ABAR-WRKY40 coupled pathway,and ABA relieves this pathway of repression by inhibiting the ABAR-CPN20 interaction to activate ABAR-WRKY40 interaction.

关键词： co-chaperonin CPN20 Mg-chelatase H subunit WRKY40 ABA signalling

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational biology and Engineering program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus