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transcriptional control of pancreaticβ-cell identity and plasticity during the pathogenesis of type 2 diabetes

Journal of Genetics and Genomics 2022年第4期49卷 316-328页

作者： Ziyin Zhang Yue Gao Zhuo-Xian Meng Department of Pathology and Pathophysiology and Department of Geriatrics of Affiliated Hangzhou First People’s Hospital Zhejiang University School of MedicineHangzhouChina Key Laboratory of Disease Proteomics of Zhejiang Province Zhejiang University School of MedicineHangzhouZhejiang310058China Department of Geriatrics Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouZhejiang310006China

Type 2 diabetes(T2D)is caused by insulin resistance and insufficient insulin *** has increasingly indicated that pancreaticβ-cell dysfunction is the primary determinant of T2D disease progression and *** plasticity is an important feature of pancreaticβ-*** T2D development,pancreaticβ-cells undergo dynamic ***β-cell death/apoptosis in later-stage T2D is the major cause ofβ-cell dysfunction,recent studies have revealed thatβ-cell dedifferentiation and reprogramming,which play critical roles inβ-cell functional regulation in the early and middle T2D progression stages,are characterized by(i)a loss of matureβ-cell-enriched genes;(ii)dedifferentiation to a progenitor-like state;and(iii)transdifferentiation into other cell *** roles of transcription factors(TFs)in the establishment and maintenance ofβ-cell identity during pancreatic development have been extensively ***,we summarize the roles and underlying mechanisms of TFs in the maintenance ofβ-cell identity under physiological and type 2 diabetic *** feasible approaches for restoring islet functions are also discussed.A better understanding of the transcriptional control ofβ-cell identity and plasticity will pave the way for developing more effective strategies,such asβ-cell regeneration therapy,to treat T2D and associated metabolic disorders.

关键词： Type 2 diabetes Pancreaticβ-cell transcription factors Dedifferentiation Transdifferentiation Redifferentiation

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WSB1 regulates c-Myc expression through β-catenin signaling and forms a feedforward circuit

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1225-1239页

作者： Xiaomeng Gao Jieqiong You Yanling Gong Meng Yuan Haiying Zhu Liang Fang Hong Zhu Meidan Ying Qiaojun He Bo Yang Ji Cao Institute of Pharmacology and Toxicology Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China The Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 310058China Department of Biology Southern University of Science and TechnologyShenzhen 518055China Cancer Center of Zhejiang University Hangzhou 310058China

The dysregulation of transcription factors is widely associated with *** the most well-defined transcription factor in multiple types of cancer,c-Myc can transform cells by transactivating various downstream *** that there is no effective way to directly inhibit c-Myc,c-Myc targeting strategies hold great potential for cancer *** this study,we found that WSB1,which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples,is a direct target gene of c-Myc,and can positively regulate c-Myc expression,which forms a feedforward circuit promoting cancer *** sequencing results from Bel-7402 cells confirmed that WSB1 promoted cMyc expression through theβ-catenin ***,WSB1 affectedβ-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptorβ-TRCP recruitment,which inhibited the ubiquitination ofβ-catenin and transactivated *** interest,the effect of WSB1 on c-Myc was independent of its E3 ligase ***,overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc ***,our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role,highlighting a potential c-Myc intervention strategy in cancer treatment.

关键词： transcription factors c-Myc WSB1 Ubiquitinationproteasome pathway β-Catenin destruction complex Feedback loop Tumorigenesis Cancer treatment

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MINI-EX:Integrative inference of single-cell gene regulatory networks in plants

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Molecular Plant 2022年第11期15卷 1807-1824页

作者： Camilla Ferrari Nicolás Manosalva Pérez Klaas Vandepoele Department of Plant Biotechnology and Bioinformatics Ghent University9052 GhentBelgium Center for Plant Systems Biology VIB9052 GhentBelgium Bioinformatics Institute Ghent Ghent University9052 GhentBelgium

Multicellular organisms,such as plants,are characterized by highly specialized and tightly regulated cell populations,establishing specific morphological structures and executing distinct *** regulatory networks(GRNs)describe condition-specific interactions of transcription factors(TFs)regulating the expression of target genes,underpinning these specific *** efficient and validated methods to identify cell-type-specific GRNs from single-cell data in plants are lacking,limiting our understanding of the organization of specific cell types in both model species and crops,we developed MINI-EX(Motif-Informed Network Inference based on single-cell EXpression data),an integrative approach to infer cell-type-specific networks in ***-EX uses single-cell transcriptomic data to define expression-based networks and integrates TF motif information to filter the inferred regulons,resulting in networks with increased ***,regulons are assigned to different cell types,leveraging cell-specific expression,and candidate regulators are prioritized using network centrality measures,functional annotations,and expression *** embedded prioritization strategy offers a unique and efficient means to unravel signaling cascades in specific cell types controlling a biological process of *** demonstrate the stability of MINI-EX toward input data sets with low number of cells and its robustness toward missing data,and show that it infers state-of-the-art networks with a better performance compared with other related single-cell network ***-EX successfully identifies key regulators controlling root development in Arabidopsis and rice,leaf development in Arabidopsis,and ear development in maize,enhancing our understanding of cell-type-specific regulation and unraveling the roles of different regulators controlling the development of specific cell types in plants.

关键词： single-cell RNA-seq gene regulatory network transcription factors systems biology

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Asymmetric cell division in plant development

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Journal of Integrative Plant Biology 2023年第2期65卷 343-370页

作者： Yi Zhang Tongda Xu Juan Dong Plant Synthetic Biology Center Haixia Institute of Science and Technologyand College of Life SciencesFujian Agriculture and Forestry UniversityFuzhou 350002 China The Waksman Institute of Microbiology Rutgersthe State University of New JerseyPiscatawayNJ 08854USA Department of Plant Biology Rutgersthe State University of New JerseyNew BrunswickNJ 08891USA

Asymmetric cell division(ACD) is a fundamental process that generates new cell types during development in eukaryotic *** plant development,post-embryonic organogenesis driven by ACD is universal and more important than in animals,in which organ pattern is preset during ***,plant development provides a powerful system to study molecular mechanisms underlying *** the past decade,tremendous progress has been made in our understanding of the key components and mechanisms involved in this important process in ***,we present an overview of how ACD is determined and regulated in multiple biological processes in plant development and compare their conservation and specificity among different model cell *** also summarize the molecular roles and mechanisms of the phytohormones in the regulation of plant ***,we conclude with the overarching paradigms and principles that govern plant ACD and consider how new technologies can be exploited to fill the knowledge gaps and make new advances in the field.

关键词： asymmetric cell division peptide signaling phytohormonal signaling polarity proteins plant development transcription factors

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The anti-cancerous mechanism of licochalcone A on human hepatoma cell HepG2 based on the miRNA omics

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Food Science and Human Wellness 2023年第4期12卷 1136-1148页

作者： Jun Wang Xiuxiu Zhang Zhijing Ni Elnur Elam Kiran Thakur Kexin Li Chuyan Wang Jianguo Zhang Zhaojun Wei School of Biological Food and Environment Hefei UniversityHefei 230601China School of Food and Biological Engineering Hefei University of TechnologyHefei 230009China School of Biological Science and Engineering Ningxia Key Laboratory for the Development and Application of Microbial Resources in Extreme EnvironmentsNorth Minzu UniversityYinchuan 750021China

To explore the function of licochalcone A as an anticancer phytochemical on HepG2 cells and investigate its potential mechanisms,we analyzed the microRNAs(miRNAs)expression profile of HepG2 cells in response to licochalcone A(70μmol/L)in vitro.102 dysregulated miRNAs were detected,and SP1 was expected as the transcription factor that regulates the functions of most screened miRNAs.A sum of 431 targets,the overlap of predicted mRNAs from TargetScan,miRDB,and miRtarbase were detected as the targets for these dysregulated *** signaling pathway was the hub pathway for the targets.A protein-protein interaction network was structured on the STRING platform to discover the hub *** them,PIK3R1,CDC42,ESR1,SMAD4,SUMO1,KRAS,AGO1,*** screened ***,the miRNA-target networks were established to screen key dysregulated *** key miRNAs(hsa-miR-133b and hsa-miR-145-5p)were ***,the miRNA-target-transcription factor networks were constructed for these key *** networks for these key miRNAs included three and two transcription factors,*** identified miRNAs,transcription factors,targets,and regulatory networks may offer hints to understand the molecular mechanism of licochalcone A as a natural anticarcinogen.

关键词： Licochalcone A HepG2 cells Dysregulated miRNAs transcription factors Targets Regulatory networks

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Phosphorylation regulation of nitrogen,phosphorus,and potassium uptake systems in plants

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The Crop Journal 2023年第4期11卷 1034-1047页

作者： Dongli Hao Xiaohui Li Weiyi Kong Rongrong Chen Jianxiu Liu Hailin Guo Jinyan Zhou The National Forestry and Grassland Administration Engineering Research Center for Germplasm Innovation and Utilization of Warm-Season Turfgrasses Jiangsu Key Laboratory for the Research and Utilization of Plant ResourcesInstitute of BotanyJiangsu Province and Chinese Academy of Sciences(Nanjing Botanical Garden Mem.Sun Yat-Sen)Nanjing 210014JiangsuChina Department of Agronomy and Horticulture Jiangsu Vocational College of Agriculture and ForestJurong 212400JiangsuChina

The uptake of ammonium,nitrate,phosphorus,and potassium ions by roots is mediated by specific ion transporter or channel proteins,and protein phosphorylation regulation events occurring on these proteins and their regulators determine their ultimate *** the mechanism by which protein phosphorylation modification regulates nutrient uptake will advance plant breeding for high nutrientuse *** this review,it is concluded that the root nutrient absorption system is composed of several,but not all,members of a specific ion transporter or channel *** nutrient-starvation conditions,protein phosphorylation-based regulation of these proteins and associated transcription factors increases ion transporter-or channel-mediated nutrient uptake capacity via direct function activity enhancement,allowing more protein trafficking to the plasma membrane,by strengthening the interaction of transporters and channels with partner proteins,by increasing their protein stability,and by transcriptional *** excessive nutrient conditions,protein phosphorylation-based regulation suppresses nutrient uptake by reversing these *** phosphorylation regulation items that increase nutrient absorption and weakening phosphorylation modification items that are not conducive to nutrient absorption show potential as strategies for increasing nutrient use efficiency.

关键词： Ammonium uptake machinery Nitrate uptake machinery Phosphate uptake machinery Potassium uptake machinery transcription factors Protein phosphorylation

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transcriptional regulation analysis reveals the complexity of metamorphosis in the Pacific oyster(Crassostrea gigas)

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Marine Life Science & Technology 2023年第4期5卷 467-477页

作者： Fei Xu Shaoxi Deng Daria Gavriouchkina Guofan Zhang CAS and Shandong Province Key Laboratory of Experimental Marine Biology Center for Ocean Mega-ScienceInstitute of OceanologyChinese Academy of SciencesQingdao 266071China Laoshan Laboratory Qingdao 266237China Shandong Technology Innovation Center of Oyster Seed Industry Qingdao 266105China School of Energy and Environment and State Key Laboratory of Marine Pollution City University of Hong KongHong Kong 999077China Molecular Genetics Unit Okinawa Institute of Science and Technology Graduate UniversityOkinawa 904-0495Japan UK Dementia Research Institute University College LondonLondon WC1E 6BTUK

Many marine invertebrate phyla are characterized by indirect *** animals transit from planktonic larvae to benthic spats via settlement and metamorphosis,which contributes to their adaption to the marine *** the biological process of metamorphosis is,thus,key to understanding the origin and evolution of indirect *** numerous studies have been conducted on the relationship between metamorphosis and the marine environment,microorganisms,and neurohormones,little is known about gene regulation network(GRN)dynamics during ***-competent pediveligers of the Pacific oyster Crassostrea gigas were assayed in this *** assaying gene expression patterns and open chromatin region changes of different samples of larvae and spats,the dynamics of molecular regulation during metamorphosis were *** results indicated significantly different gene regulation networks before,during and *** encoding membrane-integrated receptors and those related to the remodeling of the nervous system were upregulated before the initiation of *** biogenesis,e.g.,of various enzymes and structural proteins,occurred during metamorphosis as inferred from the comprehensive upregulation of the protein synthesis system post epinephrine *** downstream gene networks were then *** transcription factors,including homeobox,basic helix–loop–helix and nuclear receptors,showed different temporal response patterns,suggesting a complex GRN during the transition *** receptors,as well as their retinoid X receptor partner,may participate in the GRN controlling oyster metamorphosis,indicating an ancient role of the nuclear receptor regulation system in animal metamorphosis.

关键词： Gene regulation network Indirect development Lophotrochozoa Nuclear receptors Neurohormones Protein synthesis transcription factors

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Dendritic cells in cancer immunology

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Cellular & Molecular Immunology 2022年第1期19卷 3-13页

作者： Theresa L.Murphy Kenneth M.Murphy Department of Pathology and Immunology Washington University in St.LouisSchool of MedicineSt.LouisMO 63110USA

The clinical success of immune checkpoint therapy(ICT)has produced explosive growth in tumor immunology research because ICT was discovered through basic studies of immune *** of the current translational efforts are aimed at enhancing ICT by identifying therapeutic targets that synergize with CTLA4 or PD1/PD-L1 blockade and are solidly developed on the basis of currently accepted *** these principles through continuous basic research may help broaden translational *** this mindset,we focused this review on three threads of basic research directly relating to mechanisms underlying ***,this review covers three aspects of dendritic cell(DC)biology connected with antitumor immune responses but are not specifically oriented toward therapeutic ***,we review recent advances in the development of the cDC1 subset of DCs,identifying important features distinguishing these cells from other types of ***,we review the antigen-processing pathway called cross-presentation,which was discovered in the mid-1970s and remains an *** pathway serves an essential in vivo function unique to cDC1s and may be both a physiologic bottleneck and therapeutic ***,we review the longstanding field of helper cells and the related area of DC licensing,in which CD4 T cells influence the strength or quality of CD8 T cell *** topic is connected with ICT in some manner but is also a fundamental aspect of cell-mediated immunity directed toward intracellular pathogens.

关键词： Dendritic cells transcription factors cross-presentation tumor rejection CD4 help

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Transcriptome and carotenoid profiling of different varieties of Coffea arabica provides insights into fruit color formation

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Plant Diversity 2022年第3期44卷 322-334页

作者： Faguang Hu Xiaofei Bi Hongming Liu Xingfei Fu Yanan Li Yang Yang Xiaofang Zhang Ruirui Wu Guiping Li Yulan Lv Jiaxiong Huang Xinping Luo Rui Shi Institute of Tropical and Subtropical Cash Crops Yunnan Academy of Agricultural SciencesChina Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China Ministry of EducationSouthwest Forestry UniversityChina

The processability and ultimate quality of coffee(Coffea arabica)are determined by the composition of the matured *** basis of genetic variation in coffee fruit quality could be explained by studying color formation during fruit *** profiling was conducted on matured fruits of four *** varieties(orange colored fruits(ORF);purple colored fruits(PF);red colored fruits(RF)and yellow colored fruits(YF))to identify key color-regulating genes,biosynthesis pathways and transcription factors implicated in fruit color formation.A total of 39,938 genes were identified in the transcriptomes of the four *** *** all,2745,781 and 1224 differentially expressed genes(DEGs)were detected in YF_vs_PF,YF_vs_RF and YF_vs_ORF,respectively,with 1732 DEGs conserved among the three pairwise *** annotation of the DEGs led to the detection of 28 and 82 key genes involved in the biosynthesis of carotenoids and anthocyanins,*** transcription factors bHLH,MYB,NAC,MADS,and WRKY implicated in fruit color regulation were *** high expression levels of gene-LOC113688784(PSY),gene-LOC113730013(b-CHY),gene-LOC113728842(CCD7),gene-LOC113689681(NCED)and gene-LOC113729473(ABA2)in YF may have accounted for the yellow *** differential expression of several anthocyanin and carotenoid-specific genes in the fruits substantially account for the purple(PF),red(RF),and orange(ORF)*** study provides important insights into fruit color formation and variations in *** and will help to develop coffee varieties with specific color and quality traits.

关键词： Coffee Carotenoids Anthocyanins transcription factors Functional enrichment

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transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment

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Cellular & Molecular Immunology 2021年第3期18卷 528-538页

作者： Amania A.Sheikh Joanna R.Groom Divisions of Immunology and Molecular Immunology Walter and Eliza Hall Institute of Medical ResearchParkvilleVIC 3052Australia Department of Medical Biology University of MelbourneParkvilleVIC 3010Australia

During viral infection,immune cells coordinate the induction of inflammatory responses that clear infection and humoral responses that promote ***4^(+)T-cell differentiation sits at the center of this *** toward T-helper 1(Th1)cells mediates inflammation and pathogen clearance,while T follicular helper(Tfh)cells facilitate germinal center(GC)reactions for the generation of high-affinity antibodies and immune *** Th1 and Tfh differentiation occurs in parallel,these CD4^(+)T-cell identities are mutually exclusive,and progression toward these ends is determined via the upregulation of T-bet and Bcl6,*** lineage-defining transcription factors act in concert with multiple networks of transcriptional regulators that tip the T-bet and Bd6 axis in CD4^(+)T-cell progenitors to either a Th1 or Tfh *** is now clear that these transcriptional networks are guided by cytokine cues that are not only varied between distinct viral infections but also dynamically altered throughout the duration of ***,multiple intrinsic and extrinsic factors combine to specify the fate,plasticity,and function of Th1 and Tfh cells during ***,we review the current information on the mode of action of the lineage-defining transcription factors Bcl6 and T-bet and how they act individually and in complex to govern CD4^(+)T-cell ***,we outline the multifaceted transcriptional regulatory networks that act upstream and downstream of Bcl6 and T-bet to tip the differentiation equilibrium toward either a Tfh or Th1 fate and how these are impacted by dynamic inflammatory cues.

关键词： Cytokines Infection T follicular helper cells T-helper 1 cells transcription factors

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