Epigenetic regulators as the foundation for molecular classification of colorectal cancer

Colorectal cancer (CRC) accounts for approximately 10% of newly diagnosed cancer cases and cancer-related deaths worldwide~1. The identification of molecular subtypes of CRCs has significantly advanced treatment strategies,including targeted therapy and immunotherapy.

Coriander Genomics Database:a genomic,transcriptomic,and metabolic database for coriander

Coriander(Coriandrum sativum L.),also known as cilantro,is a globally important vegetable and spice crop.Its genome and that of carrot are models for studying the evolution of the Apiaceae family.Here,we developed the Coriander Genomics Database(CGDB,http://cgdb.bio2db.com/)to collect,store,and integrate the genomic,transcriptomic,metabolic,functional annotation,and repeat sequence data of coriander and carrot to serve as a central online platform for Apiaceae and other related plants.Using these data sets in the CGDB,we intriguingly found that seven transcription factor(TF)families showed significantly greater numbers of members in the coriander genome than in the carrot genome.The highest ratio of the numbers of MADS TFs between coriander and carrot reached 3.15,followed by those for tubby protein(TUB)and heat shock factors.As a demonstration of CGDB applications,we identified 17 TUB family genes and conducted systematic comparative and evolutionary analyses.RNA-seq data deposited in the CGDB also suggest dose compensation effects of gene expression in coriander.CGDB allows bulk downloading,significance searches,genome browser analyses,and BLAST searches for comparisons between coriander and other plants regarding genomics,gene families,gene collinearity,gene expression,and the metabolome.A detailed user manual and contact information are also available to provide support to the scientific research community and address scientific questions.CGDB will be continuously updated,and new data will be integrated for comparative and functional genomic analysis in Apiaceae and other related plants.

A growth-regulating factor 7(GRF7)-mediated gene regulatory network promotes leaf growth and expansion in sugarcane

Knowledge of the function of growth-regulating factors(GRFs)in sugarcane(Saccharum officinarum and S.spontaneum)growth and development could assist breeders in selecting desirable plant architectures.However,limited information about GRFs is available in Saccharum due to their polyploidy.In this study,22 GRFs were identified in the two species and their conserved domains,gene structures,chromosome location,and synteny were characterized.GRF7 expression varied among tissues and responded to diurnal rhythm.SsGRF7-YFP was localized preferentially in the nucleus and appears to act as a transcriptional cofactor.SsGRF7 positively regulated the size and length of rice leaves,possibly by regulating cell size and plant hormones.Of seven potential transcription factors binding to the SsGRF7 promoter in S.spontaneum,four showed positive expression patterns,and two showed negative expression patterns relative to SsGRF7.

AcWRKY28 mediated activation of AcCPK genes confers salt tolerance in pineapple(Ananas comosus)

Unfavorable environmental cues severely affect crop productivity resulting in significant economic losses to farmers. In plants, multiple regulatory genes, such as the WRKY transcription factor (TF) family, modulate the expression of defense genes. However, the role of the pineapple WRKY genes is poorly understood. Here, we studied the pineapple WRKY gene, AcWRKY28, by generating AcWRKY28 over-expressing transgenic pineapple plants. Overexpression of AcWRKY28 enhanced the salt stress resistance in transgenic pineapple lines. Comparative transcriptome analysis of transgenic and wild-type pineapple plants showed that “plant-pathogen interaction” pathway genes, including 9calcium-dependent protein kinases (CPKs), were up-regulated in AcWRKY28 over-expressing plants. Furthermore, chromatin immunoprecipitation and yeast one-hybrid assays revealed AcCPK12, AcCPK3, AcCPK8, AcCPK1, and AcCPK15 as direct targets of AcWRKY28. Consistently, the study of AcCPK12 over-expressing Arabidopsis lines showed that AcCPK12 enhances salt, drought, and disease resistance. This study shows that AcWRKY28 plays a crucial role in promoting salt stress resistance by activating the expression of AcCPK genes.

Polyploidy events shaped the expansion of transcription factors in Cucurbitaceae and exploitation of genes for tendril development

Cucurbitaceae is one of the most important plant families distributed worldwide.Transcription factors(TFs)regulate plant growth at the transcription level.Here,we performed a systematic analysis of 42641 TFs from 63 families in 14 Cucurbitaceae and 10 non-cucurbit species.Whole-genome duplication(WGD)was the dominant event type in almost all Cucurbitaceae plants.The TF families were divided into 1210 orthogroups(OGs),of which,112 were unique to Cucurbitaceae.Although the loss of several gene families was detected in Cucurbitaceae,the gene families expanded in five species that experienced a WGD event comparing with grape.Our findings revealed that the recent WGD events that had occurred in Cucurbitaceae played important roles in the expansion of most TF families.The functional enrichment analysis of the genes that significantly expanded or contracted uncovered five gene families,AUX/IAA,NAC,NBS,HB,and NF-YB.Finally,we conducted a comprehensive analysis of the TCP gene family and identified 16 tendril-related(TEN)genes in 11 Cucurbitaceae species.Interestingly,the characteristic sequence changed from CNNFYFP to CNNFYLP in the TEN gene(Bhi06M000087)of Benincasa hispida.Furthermore,we identified a new characteristic sequence,YNN,which could be used for TEN gene exploitation in Cucurbitaceae.In conclusion,this study will serve as a reference for studying the relationship between gene family evolution and genome duplication.Moreover,it will provide rich genetic resources for functional Cucurbitaceae studies in the future.

Water lilies as emerging models for Darwin’s abominable mystery

Water lilies are not only highly favored aquatic ornamental plants with cultural and economic importance but they also occupy a critical evolutionary space that is crucial for understanding the origin and early evolutionary trajectory of flowering plants.The birth and rapid radiation of flowering plants has interested many scientists and was considered‘an abominable mystery’by Charles Darwin.In searching for the angiosperm evolutionary origin and its underlying mechanisms,the genome of Amborella has shed some light on the molecular features of one of the basal angiosperm lineages;however,little is known regarding the genetics and genomics of another basal angiosperm lineage,namely,the water lily.In this study,we reviewed current molecular research and note that water lily research has entered the genomic era.We propose that the genome of the water lily is critical for studying the contentious relationship of basal angiosperms and Darwin’s‘abominable mystery’.Four pantropical water lilies,especially the recently sequenced Nymphaea colorata,have characteristics such as small size,rapid growth rate and numerous seeds and can act as the best model for understanding the origin of angiosperms.The water lily genome is also valuable for revealing the genetics of ornamental traits and will largely accelerate the molecular breeding of water lilies.

Optimization of protoplast isolation,transformation and its application in sugarcane (Saccharum spontaneum L.)

Sugarcane is a prominent source of sugar and ethanol production.Genetic analysis for trait improvement of sugarcane is greatly hindered by its complex genome,long breeding cycle,and recalcitrance to genetic transformation.The protoplast-based transient transformation system is a versatile and convenient tool for in vivo functional gene analysis;however,quick and effective transformation systems are still lacking for sugarcane.Here,we developed an efficient protoplast-based transformation system by optimizing conditions of protoplasts isolation and PEG-mediated transformation in S.spontaneum.The yield of viable protoplasts was approximately 1.26×107 per gram of leaf material,and the transformation efficiency of 80.19%could be achieved under the optimized condition.Furthermore,using this approach,the nuclear localization of an ABI5-like bZIPs transcription factor was validated,and the promoter activity of several putative DNase I hypersensitive sites(DHSs)was assessed.The results indicated this system can be conveniently applied to protein subcellular localization and promoter activity assays.A highly efficient S.spontaneum mesophyll cell protoplast isolation and transient transformation method was developed,and it shall be suitable for in vivo functional gene analysis in sugarcane.

Genome-wide development of interspecific microsatellite markers for Saccharum officinarum and Saccharum spontaneum

Sugarcane has a large,complex,polyploid genome that has hindered the progress of genomic research and molecular marker-assisted selection.The user-friendly SSR markers have attracted considerable attention owing to their ideal genetic attributes.However,these markers were not characterized and developed at the genome-wide scale due to the previously lacking high-quality chromosome-level assembled sugarcane genomes.In this present study,744305and 361638 candidate SSRs were identified from the genomes of S.officinarum and S.spontaneum,respectively.We verified the reliability of the predicted SSRs by using 1200 interspecific SSR primer pairs to detect polymorphisms among 11 representative accessions of Saccharum,including S.spontaneum,S.officinarum,S.robustum,and modern sugarcane hybrid.The results showed that 660 SSR markers displayed interspecific polymorphisms among these accessions.Furthermore,100 SSRs were randomly selected to detect the genetic diversity for 39 representative Saccharum accessions.A total of 320 alleles were generated using 100 polymorphic primers,with each marker ranging from two to seven alleles.The genetic diversity analysis revealed that these accessions were distributed in four main groups,including group I(14 S.spontaneum accessions),group II(two S.officinarum accessions),group III(18 modern sugarcane hybrid accessions),and group IV(five S.robustum accessions).Experimental verification supported the reliability of the SSR markers based on genome-wide predictions.The development of a large number of SSR markers based on wet experiments is valuable for genetic studies,including genetic linkage maps,comparative genome analysis,genome-wide association studies,and marker-assisted selection in Saccharum.

PGD: Pineapple Genomics Database

Pineapple occupies an important phylogenetic position as its reference genome is a model for studying the evolution the Bromeliaceae family and the crassulacean acid metabolism(CAM)photosynthesis.Here,we developed a pineapple genomics database(PGD,http://pineapple.angiosperms.org/pineapple/html/index.html)as a central online platform for storing and integrating genomic,transcriptomic,function annotation and genetic marker data for pineapple(Ananas comosus(L.)Merr.).The PGD currently hosts significant search tools and available datasets for researchers to study comparative genomics,gene expression,gene co-expression molecular marker,and gene annotation of A.comosus(L).PGD also performed a series of additional pages for a genomic browser that visualizes genomic data interactively,bulk data download,a detailed user manual,and data integration information.PGD was developed with the capacity to integrate future data resources,and will be used as a long-term and open access database to facilitate the study of the biology,distribution,and the evolution of pineapple and the relative plant species.An email-based helpdesk is also available to offer support with the website and requests of specific datasets from the research community.

Somatic DNA copy number alterations and their potential clinical utility for predicting lethal prostate cancer

Current clinicopathologic indicators are insufficient to distinguish the small percentage of aggressive prostate cancer （PCa） from the vast majority of indolent disease at diagnosis, leading to overtreatment of PCa. A recent study reported and confirmed a strong association of PCa-specific mortality with somatic DNA copy number alterations （CNAs） in primary pro- state tumors.

Species-specific regulatory pathways of small RNAs play sophisticated roles in flower development in Dimocarpus longan Lour.

Flower development plays vital role in horticultural plants.Post-transcriptional regulation via small RNAs is important for plant flower development.To uncover post-transcriptional regulatory networks during the flower development in Dimocarpus longan Lour.‘Shixia’,an economically important fruit crop in subtropical regions,we collected and analyzed sRNA deep-sequencing datasets and degradome libraries Apart from identifying miRNAs and phased siRNA generating loci(PHAS loci),120 hairpin loci,producing abundant sRNAs,were identified by in-house protocols.Our results suggested that 56 miRNA-target pairs,2221-nt-PHAS loci,and 111 hairpin loci are involved in posttranscriptional gene silencing during longan reproductive development.Lineage-specific or species-specific post-transcriptional regulatory modules have been unveiled,including miR482-PHAS and miRN15.miR482-PHAS might be involved in longan flower development beyond their conserved roles in plant defense,and miRN15 is a novel miRNA likely associated with a hairpin locus(HPL-056)to regulate strigolactone receptor gene DWARF14(D14)and the biogenesis of phasiRNAs from D14.These small RNAs are enriched in flower buds,suggesting they are likely involved in post-transcriptional regulatory networks essential for longan flower development via the strigolactone signaling pathway.

A likely autotetraploidization event shaped the Chinese mahogany(Toona sinensis)genome

Chinese mahogany(Toona sinensis) is of considerable medical and economic importance, and its genome has been deciphered. However, the process underlying its polyploidy is unclear, and the chromosomal evolutionary trajectory is poorly understood. Here, by reanalysing the T.sinensis genome, we found evidence of a tetraploidization event(T. sinensis special tetraploidization, TST) that occurred approximately 15-17 million years ago(MYA) after the core eudicot-common hexaploidization(ECH or gamma) event. We characterized the synonymous nucleotide substitution rates(Ks values) of collinear genes and found that T. sinensis genes affected by the TST evolve at a slower rate than Acer yangbiense genes. Furthermore, we identified homologous genes related to polyploidization and speciation and constructed multiple alignments with different reference genomes. Notably, the significant balance of gene retention and loss characterized in the two TST-derived subgenomes suggests an autopolyploid nature of the TST. Moreover, we deduced the chromosomal karyotypes of the two subgenomes and identified 7chromosomal fusions that have shaped the T. sinensis genome;more information is available on a newly constructed karyotype platform(http://www.cgrpoee.top/Toona_sinensis/index.html). The T. sinensis genome preserves the ancestral chromosome structure of dicotyledons well and could serve as a good reference for understanding genomic changes in other Meliaceae and Sapindales plants. In addition, we verified that tandem duplication and the ECH have promoted the expansion of terpene synthase(TPS) genes;conversely, the TST seems to have inhibited expansion of these genes. This present effort has clarified the polyploidy events of the T. sinensis genome, filled gaps in the history of karyotype evolution, and laid a solid foundation for further genomic studies in the Meliaceae research community and beyond.

Macroalgal deep genomics illuminate multiple paths to aquatic,photosynthetic multicellularity

Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularity phenotypes.However,their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain uncharacterized.In this study,we sequenced 110 macroalgal genomes from diverse climates and phyla,and identified key genomic features that distinguish them from their microalgal relatives.Genes for cell adhesion,extracellular matrix formation,cell polarity,transport,and cell differentiation distinguish macroalgae from microalgae across all three major phyla,constituting conserved and unique gene sets supporting multicellular processes.Adhesome genes show phylum-and climate-specific expansions that may facilitate niche adaptation.Collectively,our study reveals genetic determinants of convergent and divergent evolutionary trajectories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.

Two-step model of paleohexaploidy, ancestral genome reshuffling and plasticity of heat shock response in Asteraceae

An ancient hexaploidization event in the most but not all Asteraceae plants,may have been responsible for shaping the genomes of many horticultural,ornamental,and medicinal plants that promoting the prosperity of the largest angiosperm family on the earth.However,the duplication process of this hexaploidy,as well as the genomic and phenotypic diversity of extant Asteraceae plants caused by paleogenome reorganization,are still poorly understood.We analyzed 11 genomes from 10 genera in Asteraceae,and redated the Asteraceae common hexaploidization(ACH)event∼70.7–78.6 million years ago(Mya)and the Asteroideae specific tetraploidization(AST)event∼41.6–46.2 Mya.Moreover,we identified the genomic homologies generated from the ACH,AST and speciation events,and constructed a multiple genome alignment framework for Asteraceae.Subsequently,we revealed biased fractionations between the paleopolyploidization produced subgenomes,suggesting the ACH and AST both are allopolyplodization events.Interestingly,the paleochromosome reshuffling traces provided clear evidence for the two-step duplications of ACH event in Asteraceae.Furthermore,we reconstructed ancestral Asteraceae karyotype(AAK)that has 9 paleochromosomes,and revealed a highly flexible reshuffling of Asteraceae paleogenome.Of specific significance,we explored the genetic diversity of Heat Shock Transcription Factors(Hsfs)associated with recursive whole-genome polyploidizations,gene duplications,and paleogenome reshuffling,and revealed that the expansion of Hsfs gene families enable heat shock plasticity during the genome evolution of Asteraceae.Our study provides insights on polyploidy and paleogenome remodeling for the successful establishment of Asteraceae,and is helpful for further communication and exploration of the diversification of plant families and phenotypes.

Epigenetic modification mechanisms of chloroplasts mutants in pineapple leaves during somatic regeneration

Somaclonal variation in tissue culture is a common phenomenon induced by various external or internal environmental conditions,resulting in heritable or non-heritable alterations in gene expression. One crucial mechanism involved in plant growth and development is epigenetic regulation. A highly dynamic epigenome can respond to environmental changes by regulating gene expression. DNA methylation is one of these epigenetic modifications that can alter gene expression in tissue-cultured pineapple plants. The underlying mechanism of such somaclonal variations in pineapple and the epigenetic regulation involvement in somaclonal variations has not been studied. This study performed DNA methylome and transcriptome sequencing of wild-type(WT) and mutant pineapple plants(WS, HW, and TW). We observed altered DNA methylation patterns in chlorophyll development in the mutants. Specifically, we noticed that the methylation levels in the CHG and CHH contexts were lower in the gene body regions compared to the upstream and downstream regions. We identified several thousand differentially methylated regions(DMRs) located at the gene body regions, some of which overlapped with the differentially expressed genes(DEGs). Functional enrichment analyses suggested that these genes were involved in chlorophyll metabolism. Thus, our results revealed that the transcriptional regulation of many chlorophyll metabolic essential genes could be regulated by DNA methylation caused by somaclonal variations and provided insights into epigenetic mechanisms underlying the regulation of chlorosis in pineapple plants.

Chromosome-scale genome sequence of Suaeda glauca sheds light on salt stress tolerance in halophytes

Soil salinity is a growing concern for global crop production and the sustainable development of humanity.Therefore,it is crucial to comprehend salt tolerance mechanisms and identify salt-tolerance genes to enhance crop tolerance to salt stress.Suaeda glauca,a halophyte species well adapted to the seawater environment,possesses a unique ability to absorb and retain high salt concentrations within its cells,particularly in its leaves,suggesting the presence of a distinct mechanism for salt tolerance.In this study,we performed de novo sequencing of the S.glauca genome.The genome has a size of 1.02 Gb(consisting of two sets of haplotypes)and contains 54761 annotated genes,including alleles and repeats.Comparative genomic analysis revealed a strong synteny between the genomes of S.glauca and Beta vulgaris.Of the S.glauca genome,70.56%comprises repeat sequences,with retroelements being the most abundant.Leveraging the allele-aware assembly of the S.glauca genome,we investigated genome-wide allele-specific expression in the analyzed samples.The results indicated that the diversity in promoter sequences might contribute to consistent allele-specific expression.Moreover,a systematic analysis of the ABCE gene families shed light on the formation of S.glauca’s flower morphology,suggesting that dysfunction of A-class genes is responsible for the absence of petals in S.glauca.Gene family expansion analysis demonstrated significant enrichment of Gene Ontology(GO)terms associated with DNA repair,chromosome stability,DNA demethylation,cation binding,and red/far-red light signaling pathways in the co-expanded gene families of S.glauca and S.aralocaspica,in comparison with glycophytic species within the chenopodium family.Time-course transcriptome analysis under salt treatments revealed detailed responses of S.glauca to salt tolerance,and the enrichment of the transition-upregulated genes in the leaves associated with DNA repair and chromosome stability,lipid biosynthetic process,and isoprenoid metabolic process.Additionally,genome-wide analysis of transcription factors indicated a significant expansion of FAR1 gene family.However,further investigation is needed to determine the exact role of the FAR1 gene family in salt tolerance in S.glauca.

Taxonomic revision of genus Rohanixalus(Anura:Rhacophoridae)in China with description of one new species

DEAR EDITOR,Based upon morphological and molecular evidence,the authors revised the genus Rohanixalus Biju,Garg,Gokulakrishnan,Chandrakasan,Thammachoti,Ren,Gopika,Bisht,Hamidy and Shouche,2020(Anura:Rhacophoridae)in China through describing one new species,adding one species to the fauna(R.shyamrupus)and supplementing data on one species(Rohanixalus hansenae;Supplementary Materials).

GametesOmics:A Comprehensive Multi-omics Database for Exploring the Gametogenesis in Humans and Mice

Gametogenesis plays an important role in the reproduction and evolution of species.The transcriptomic and epigenetic alterations in this process can influence the reproductive capacity,fertilization,and embryonic development.The rapidly increasing single-cell studies have provided valuable multi-omics resources.However,data from different layers and sequencing platforms have not been uniformed and integrated,which greatly limits their use for exploring the molecular mechanisms that underlie oogenesis and spermatogenesis.Here,we develop GametesOmics,a comprehensive database that integrates the data of gene expression,DNA methylation,and chromatin accessibility during oogenesis and spermatogenesis in humans and mice.GametesOmics provides a user-friendly website and various tools,including Search and Advanced Search for querying the expression and epigenetic modification(s)of each gene;Tools with Differentially expressed gene(DEG)analysis for identifying DEGs,Correlation analysis for demonstrating the genetic and epigenetic changes,Visualization for displaying single-cell clusters and screening marker genes as well as master transcription factors(TFs),and MethylView for studying the genomic distribution of epigenetic modifications.GametesOmics also provides Genome Browser and Ortholog for tracking and comparing gene expression,DNA methylation,and chromatin accessibility between humans and mice.GametesOmics offers a comprehensive resource for biologists and clinicians to decipher the cell fate transition in germ cell development,and can be accessed at http://gametesomics.cn/.

软件预测和MAST技术筛选mRNA反义核酸靶点的比较

基因mRNA的结构靶点筛选是反义核酸药物研发的一个难题 .兔 (Oryctolaguscuniculus) β珠蛋白基因mRNA的结构靶位点通过运用MAST技术筛选获得 ,和计算机软件RNAstructure3 71模拟分析的位点进行了比较 ,也和寡核苷酸微阵列杂交技术筛选获得的靶点结果 (M .Natalie ,1 997)进行了比较 ,显示 :据MAST技术获得的兔 β珠蛋白基因 2个反义核酸结合靶位点 ,和用RNAstructure3 71软件给出的模拟分析的 2个靶位点相同 ,且它们与寡核苷酸微阵列杂交技术的结果完全一致 .运用MAST技术筛选获得绿色荧光蛋白 (GFP)mRNA有 4个结构靶位点 ,体外分析表明这 4个靶位点均有效 ,其中有 3个与RNAstructure3 71软件分析的靶点相同 ,但计算机模拟推荐的结构靶位点较多 ,而且随着基因长度增加确认靶位点的难度增大 ,获得的靶位点还需要实验验证 ,计算机软件模拟分析对实验筛选靶点、设计反义核酸有辅助价值 .MAST方法能筛选各种长度基因mRNA的全部可及位点和准确给定核苷酸的起止位置以供设计反义核酸 ,具有简单快捷的优点 ,将能为反义核酸设计起重要作用 .

Role of the tissue microenvironment as a therapeutic target in hepatocellular carcinoma

Hepatocellular carcinoma is difficult to treat,primarilybecause the underlying molecular mechanisms drivingclinical outcome are still poorly understood.Growingevidence suggests that the tissue microenvironmenthas a role in the biological behavior of the tumor.Themain clinical issue is to identify the best target fortherapeutic approaches.Here,we discuss the hypothesis that the entire tissue microenvironment might beconsidered as a biological target.However,the tissuemicroenvironment consists of several cellular and biochemical components,each of which displays a distinctbiological activity.We discuss the major components ofthis environment and consider how they may interactto promote tumor/host crosstalk.