Aegilops speltoides,the closest ancestor of the wheat B subgenome,has been well studied genomically.However,the epigenetic landscape of Ae.speltoides and the effects of epigenetics on its growth and development remain...Aegilops speltoides,the closest ancestor of the wheat B subgenome,has been well studied genomically.However,the epigenetic landscape of Ae.speltoides and the effects of epigenetics on its growth and development remain poorly understood.Here,we present a comprehensive multi-omics atlas of leaves and roots in Ae.speltoides,encompassing transcriptome,DNA methylation,histone modifications,and small RNA profiling.Divergent DNA methylation levels were detected between leaves and roots,and were associated with differences in accumulated 24-nt siRNAs.DNA methylation changes in promoters and gene bodies showed strong connections with altered expression between leaves and roots.Transcriptional regulatory networks(TRN)reconstructed between leaves and roots were driven by tissue-specific TF families.DNA methylation and histone modification act together as switches that shape root and leaf morphogenesis by modulating the binding of tissue-specific TFs to their target genes.The TRNs in leaves and roots reshaped during wheat polyploidization were associated with alterations in epigenetic modi-fications.Collectively,these results not only shed light on the critical contribution of epigenetic regulation in the morphogenesis of leaves and roots in Ae.speltoides but also provide new insights for future investigations into the complex interplay of genetic and epigenetic factors in the developmental biology of common wheat.展开更多
Metabolic dysfunction-associated steatotic liver disease,characterized by pathological intracellular triglyceride(TG)accumulation,is mechanistically associated with the disrupted spatiotemporal regulation of hepatocyt...Metabolic dysfunction-associated steatotic liver disease,characterized by pathological intracellular triglyceride(TG)accumulation,is mechanistically associated with the disrupted spatiotemporal regulation of hepatocyte nuclear factor(HNF)-dependent transcriptional programs.HNFs,including key members such as HNF-1α,HNF-4α,and HNF-6,constitute a liver-enriched family of transcription factors that govern hepatic lipid metabolism through hierarchical transcriptional regulatory networks.These networks critically regulate the dynamic equilibrium of TG metabolism,encompassing TG synthesis,storage,lipolysis,and lipoprotein-mediated export.This review comprehensively deciphers the molecular cascades through which HNF dysfunction exacerbates TG metabolic disorder in metabolic dysfunction-associated steatotic liver disease.Additionally,we evaluate emerging translational strategies targeting key HNF regulatory nodes and discuss current clinical challenges as well as potential solutions.展开更多
Salt stress is a global constraint on agricultural production.Therefore,the development of salt tolerant plants has become a current research hotspot.While salt tolerance has evolved more frequently in C_(4) grass lin...Salt stress is a global constraint on agricultural production.Therefore,the development of salt tolerant plants has become a current research hotspot.While salt tolerance has evolved more frequently in C_(4) grass lineages,few studies have explored the molecular bases underlying salt stress tolerance in the C_(4) crop foxtail millet.In this study,we used a multi-pronged approach spanning the omics analyses of transcriptomes and physiological analysis of the C_(3) crop rice and the C_(4) model crop foxtail millet to investigate their responses to salt stress.The results revealed that compared to C_(3) rice,C_(4) foxtail millet has upregulated abscisic acid(ABA)and notably reduced CK biosynthesis and signaling transduction under salt stress.Salt stress in C_(3) rice plants triggered rapid downregulation of photosynthesis related genes,which was coupled with severely reduced net photosynthetic rates.In the salt-treated C_(3) rice and C_(4) foxtail millet,some stress responsive transcription factors(TFs),such as AP2/ERF,WRKY and MYB,underwent strong and distinct transcriptional changes.Based on a weighted gene co-expression network analysis(WGCNA),the AP2/ERF transcription factor Rice Starch Regulator1 SiRSR1(Seita.3G044600)was identified as a key regulator of the salt stress response.To confirm its function,we generated OsRSR1-knockout lines using CRISPR/Cas9 genome editing in rice and its upstream repressor SimiR172a-overexpressing(172a-OE)transgenic plants in foxtail millet,which both showed increased salt tolerance.Overall,this study not only provides new insights into the convergent regulation of the salt stress responses of foxtail millet and rice,but it also sheds light on the divergent signaling networks between them in response to salt stress.展开更多
Primary biliary cholangitis(PBC) is an autoimmune disease involving dysregulation of a broad array of homeostatic and metabolic processes. Although considerable single-nucleotide polymorphisms have been unveiled, a la...Primary biliary cholangitis(PBC) is an autoimmune disease involving dysregulation of a broad array of homeostatic and metabolic processes. Although considerable single-nucleotide polymorphisms have been unveiled, a large fraction of risk factors remains enigmatic. Candidate genes with rare mutations that tend to confer more deleterious effects need to be identified. To help pinpoint cellular and developmental mechanisms beyond common noncoding variants, we integrate whole exome sequencing with integrative network analysis to investigate genes harboring de novo mutations. Prominent convergence has been revealed on a network of disease-specific co-expression comprised of 55 genes associated with homeostasis and metabolism. The transcription factor gene MEF2 D and the DNA repair gene PARP2 are highlighted as hub genes and identified to be up-and down-regulated, respectively, in peripheral blood data set. Enrichment analysis demonstrates that altered expression of MEF2 D and PARP2 may trigger a series of molecular and cellular processes with pivotal roles in PBC pathophysiology. Our study identifies genes with de novo mutations in PBC and suggests that a subset of genes in homeostasis and metabolism tend to act in synergy through converging on co-expression network, providing novel insights into the etiology of PBC and expanding the pool of molecular candidates for discovering clinically actionable biomarkers.展开更多
Highly heterogeneous acute myeloid leukemia(AML)exhibits dysregulated transcriptional programs.Transcription factor(TF)regulatory networks underlying AML subtypes have not been elucidated at single-cell resolution.Her...Highly heterogeneous acute myeloid leukemia(AML)exhibits dysregulated transcriptional programs.Transcription factor(TF)regulatory networks underlying AML subtypes have not been elucidated at single-cell resolution.Here,we comprehensively mapped malignancy-related TFs activated in different AML subtypes by analyzing single-cell RNA sequencing data from AMLs and healthy donors.We first identified six modules of regulatory networks which were prevalently dysregulated in all AML patients.AML subtypes featured with different malignant cellular composition possessed subtype-specific regulatory TFs associated with differentiation suppression or immune modulation.At last,we validated that ERF was crucial for the development of hematopoietic stem/progenitor cells by performing loss-and gain-of-function experiments in zebrafish embryos.Collectively,our work thoroughly documents an abnormal spectrum of transcriptional regulatory networks in AML and reveals subtype-specific dysregulation basis,which provides a prospective view to AML pathogenesis and potential targets for both diagnosis and therapy.展开更多
Determining how cells regulate their transcriptional response toextracellular signals is key to the understanding of complex eukaryotic systems. This study wasinitiated with the goals of furthering the study of mammal...Determining how cells regulate their transcriptional response toextracellular signals is key to the understanding of complex eukaryotic systems. This study wasinitiated with the goals of furthering the study of mammalian transcriptional regulation andanalyzing the relative benefits of related computational methodologies. One dataset available forsuch an analysis involved gene expression profiling of the early growth factor response to plateletderived growth factor (PDGF) in a human glioblastoma cell line; this study differentiated geneswhose expression was regulated by signaling through the phosphoinositide-3-kinase (PI3K) versus theextracellular-signal regulated kinase (ERK) pathways. We have compared the inferred transcriptionfactors from this previous study with additional predictions of regulatory transcription factorsusing two alternative promoter sequence analysis techniques. This comparative analysis, in which thealgorithms predict overlapping, although not identical, sets of factors, argues for meticulousbenchmarking of promoter sequence analysis methods to determine the positive and negative attributesthat contribute to their varying results. Finally, we inferred transcriptional regulatory networksderiving from various signaling pathways using the CARRIE program suite. These networks not onlyincluded previously described transcriptional features of the response to growth signals, but alsopredicted new regulatory features for the propagation and modulation of the growth signal.展开更多
Phenotypic plasticity plays fundamental roles in successful adaptation of animals in response to environmental variations.Here,to reveal the transcriptome reprogramming in locust phase change,a typical phenotypic plas...Phenotypic plasticity plays fundamental roles in successful adaptation of animals in response to environmental variations.Here,to reveal the transcriptome reprogramming in locust phase change,a typical phenotypic plasticity,we conducted a comprehensive analysis of multiple phase-related transcriptomic datasets of the migratory locust.We defined PhaseCore genes according to their contribution to phase differentiation by the adjustment for confounding principal components analysis algorithm(AC-PCA).Compared with other genes,PhaseCore genes predicted phase status with over 87.5%accuracy and displayed more unique gene attributes including the faster evolution rate,higher CpG content and higher specific expression level.Then,we identified 20 transcription factors(TFs)named PhaseCoreTF genes that are associated with the regulation of PhaseCore genes.Finally,we experimentally verified the regulatory roles of three representative TFs(Hr4,Hr46,and grh)in phase change by RNAi.Our findings revealed that core transcriptional signatures are involved in the global regulation of locust phase changes,suggesting a potential common mechanism underlying phenotypic plasticity in insects.The expression and network data are accessible in an online resource called LocustMine(http://www.locustmine.org:8080/locustmine).展开更多
Tension wood(TW)is a specialized xylem tissue formed in angiosperm trees under gravitational stimulus or mechanical stresses(e.g.,bending).The genetic regulation that underlies this important mechanism remains poorly ...Tension wood(TW)is a specialized xylem tissue formed in angiosperm trees under gravitational stimulus or mechanical stresses(e.g.,bending).The genetic regulation that underlies this important mechanism remains poorly understood.Here,we used laser capture microdissection of stem xylem cells coupled with full transcriptome RNA-sequencing to analyze TW formation in Populus trichocarpa.After tree bending,PtrLBD39 was the most significantly induced transcription factor gene;it has a phylogenetically paired homolog,PtrLBD22.CRISPR-based knockout of PtrLBD39/22 severely inhibited TW formation,reducing cellulose and increasing lignin content.Transcriptomic analyses of CRISPR-based PtrLBD39/22 double mutants showed that these two genes regulate a set of TW-related genes.Chromatin immunoprecipitation sequencing(ChIP-seq)was used to identify direct targets of PtrLBD39.We integrated transcriptomic analyses and ChIP-seq assays to construct a transcriptional regulatory network(TRN)mediated by PtrLBD39.In this TRN,PtrLBD39 directly regulates 26 novel TW-responsive transcription factor genes.Our work suggests that PtrLBD39 and PtrLBD22 specifically control TW formation by mediating a TW-specific TRN in Populus.展开更多
Metabolism is regulated at multiple levels in response to the changes of internal or external conditions. Transcriptional regulation plays an important role in regulating many metabolic reactions by altering the conce...Metabolism is regulated at multiple levels in response to the changes of internal or external conditions. Transcriptional regulation plays an important role in regulating many metabolic reactions by altering the concentrations of metabolic enzymes. Thus, integration of the transcriptional regulatory information is necessary to improve the accuracy and predictive ability of metabolic models. Here we review the strategies for the reconstruction of a transcriptional regulatory network （TRN） for yeast and the integration of such a reconstruction into a flux balance analysis-based metabolic model. While many large-scale TRN reconstructions have been reported for yeast, these reconstructions still need to be improved regarding the functionality and dynamic property of the regulatory interactions. In addition, mathematical modeling approaches need to be further developed to efficiently integrate transcriptional regulatory interactions to genome-scale metabolic models in a quantitative manner.展开更多
Because cereal kernel texture is a determinant of maize end-use properties,it is desirable to elucidate the genetic control of kernel formation and thereby to optimize maize kernel texture for breeding.Basically,maize...Because cereal kernel texture is a determinant of maize end-use properties,it is desirable to elucidate the genetic control of kernel formation and thereby to optimize maize kernel texture for breeding.Basically,maize kernel texture is determined by the ratio of vitreous endosperm in the peripheral region to the floury endosperm in the center of the kernel.In contrast to the puroindoline proteins(Pins)as the major determinants of grain texture specific to wheat,maize kernel texture is a quantitative trait that is controlled by many minor-effect genes.Nonetheless,substantial progresses have been made in unravelling gene regulatory networks underlying maize kernel formation that is related to its texture.Here,we review the current knowledge on maize endosperm development,focusing on vitreous and floury endosperm formation,and summarize the potential transcription regulatory mechanisms for starch and zein biosynthesis.The integration of the information will potentially provide valuable candidate genes for breeding maize varieties with improved kernel texture and quality.展开更多
Nickel(Ni),a component of urease,is a micronutrient essential for plant growth and development,but excess Ni is toxic to plants.Tomato(Solanum lycopersicum L.)is one of the important vegetables worldwide.Excessive use...Nickel(Ni),a component of urease,is a micronutrient essential for plant growth and development,but excess Ni is toxic to plants.Tomato(Solanum lycopersicum L.)is one of the important vegetables worldwide.Excessive use of fertilizers and pesticides led to Ni contamination in agricultural soils,thus reducing yield and quality of tomatoes.However,the molecular regulatory mechanisms of Ni toxicity responses in tomato plants have largely not been elucidated.Here,we investigated the molecular mechanisms underlying the Ni toxicity response in tomato plants by physiobiochemical,transcriptomic and molecular regulatory network analyses.Ni toxicity repressed photosynthesis,induced the formation of brush-like lateral roots and interfered with micronutrient accumulation in tomato seedlings.Ni toxicity also induced reactive oxygen species accumulation and oxidative stress responses in plants.Furthermore,Ni toxicity reduced the phytohormone concentrations,including auxin,cytokinin and gibberellic acid,thereby retarding plant growth.Transcriptome analysis revealed that Ni toxicity altered the expression of genes involved in carbon/nitrogen metabolism pathways.Taken together,these results provide a theoretical basis for identifying key genes that could reduce excess Ni accumulation in tomato plants and are helpful for ensuring food safety and sustainable agricultural development.展开更多
Identification of all genes involved in the phytochrome （phy）-medieted responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth end developm...Identification of all genes involved in the phytochrome （phy）-medieted responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth end development. This article highlights end integrates the central findings of two recent comprehensive studies in Arabidopsis that have identified the genome-wide set of phy-reguleted genes that respond rapidly to red-light signals upon first exposure of dark-grown seedlings, and have tested the functional relevance to normal seedling photomorphogenesis of an Initial subset of these genes. The data： （a） reveal considerable complexity in the channeling of the light signals through the different phy-femily members （phyA to phyE） to responsive genes; （b） identify a diversity of transcription-factor-encoding genes as major early, if not primary, targets of phy signaling, end, therefore, as potentially important regulators in the transcriptional-network hierarchy; and （c） identify auxin-related genes as the dominant class among rapidly-regulated, hormone-related genes. However, reverse-genetic functional profiling of a selected subset of these genes reveals that only a limited fraction are necessary for optimal phy-induced seedling deetioletion.展开更多
During the floral transition the shoot apical meristem changes its identity from a vegetative to an inflorescence state. This change in identity can be promoted by external signals, such as inductive photoperiod condi...During the floral transition the shoot apical meristem changes its identity from a vegetative to an inflorescence state. This change in identity can be promoted by external signals, such as inductive photoperiod conditions or vernalization, and is accompanied by changes in expression of key developmental genes. The change in meristem identity is usually not reversible, even if the inductive signal occurs only transiently. This implies that at least some of the key genes must possess an intrinsic memory of the newly acquired expression state that ensures irreversibility of the process. In this review, we discuss different molecular scenarios that may underlie a molecular memory of gene expression.展开更多
The construction of a secondary cell wall is an important and necessary developmental decision that sup- ports cell function and plant stature. Unlike the primary cell walls, which are initiated during cell division a...The construction of a secondary cell wall is an important and necessary developmental decision that sup- ports cell function and plant stature. Unlike the primary cell walls, which are initiated during cell division and develop along with the expansion of the cells, secondary cell walls are constructed after the cells have stopped growing. Hence, the transition from primary to secondary wall synthesis marks an important and distinct metabolic investment by the plant. This transition requires a coordi- nated change of a plethora of cellular processes, including hormonal, transcriptional and post-transcriptional activi- ties, metabolic flux re-distributions and enzymatic activities. In this review, we briefly summarize the hormonal and transcriptional control of the primary to secondary wall transition, and highlight important gaps in our under- standing of the metabolic framework that support the transition. Several tools that may aid in future research efforts to better understand the changes in cell wall synthesis during the trans-differentiation are also discussed.展开更多
Recent breakthroughs in transcriptome analysis and gene characterization have provided valuable resources and information about the maize endosperm developmental program.The high temporal-resolution transcriptome anal...Recent breakthroughs in transcriptome analysis and gene characterization have provided valuable resources and information about the maize endosperm developmental program.The high temporal-resolution transcriptome analysis has yielded unprecedented access to information about the genetic control of seed development.Detailed spatial transcriptome analysis using laser-capture microdissection has revealed the expression patterns of specific populations of genes in the four major endosperm compartments:the basal endosperm transfer layer(BETL),aleurone layer(AL),starchy endosperm(SE),and embryo-surrounding region(ESR).Although the overall picture of the transcriptional regulatory network of endosperm development remains fragmentary,there have been some exciting advances,such as the identification of OPAQUE11(O11)as a central hub of the maize endosperm regulatory network connecting endosperm development,nutrient metabolism,and stress responses,and the discovery that the endosperm adjacent to scutellum(EAS)serves as a dynamic interface for endosperm-embryo crosstalk.In addition,several genes that function in BETL development,AL differentiation,and the endosperm cell cycle have been identified,such as ZmSWEET4c,Thk1,and Dek15,respectively.Here,we focus on current advances in understanding the molecular factors involved in BETL,AL,SE,ESR,and EAS development,including the specific transcriptional regulatory networks that function in each compartment during endosperm development.展开更多
Lineage commitment of thymocytes can be distinguished and modulated by key factors of transcriptional networks,such as the antagonistic expression and function of Th-POK and Runx3 in the CD4 and CD8 lineages1 and Foxp...Lineage commitment of thymocytes can be distinguished and modulated by key factors of transcriptional networks,such as the antagonistic expression and function of Th-POK and Runx3 in the CD4 and CD8 lineages1 and Foxp32 and PLZF3 in CD4^(+)regulatory T(Treg)cells and natural killer T(NKT)cells,respectively.展开更多
基金supported by the National Key Research and Development Program of China(2023YFD1200403).
文摘Aegilops speltoides,the closest ancestor of the wheat B subgenome,has been well studied genomically.However,the epigenetic landscape of Ae.speltoides and the effects of epigenetics on its growth and development remain poorly understood.Here,we present a comprehensive multi-omics atlas of leaves and roots in Ae.speltoides,encompassing transcriptome,DNA methylation,histone modifications,and small RNA profiling.Divergent DNA methylation levels were detected between leaves and roots,and were associated with differences in accumulated 24-nt siRNAs.DNA methylation changes in promoters and gene bodies showed strong connections with altered expression between leaves and roots.Transcriptional regulatory networks(TRN)reconstructed between leaves and roots were driven by tissue-specific TF families.DNA methylation and histone modification act together as switches that shape root and leaf morphogenesis by modulating the binding of tissue-specific TFs to their target genes.The TRNs in leaves and roots reshaped during wheat polyploidization were associated with alterations in epigenetic modi-fications.Collectively,these results not only shed light on the critical contribution of epigenetic regulation in the morphogenesis of leaves and roots in Ae.speltoides but also provide new insights for future investigations into the complex interplay of genetic and epigenetic factors in the developmental biology of common wheat.
基金Supported by the Science and Technology Planning Projects of Guizhou Province,No.QKHJC-MS[2025]384the Science and Technology Planning Projects of Zunyi City,No.ZSKHHZ(2023)470+3 种基金the WBE Liver Fibrosis Foundation,No.CFHPC2025028Chinese Foundation for Hepatitis Prevention and Control Muxin Research Fund of Chronic Hepatitis B,No.MX202404Beijing Liver and Gallbladder Mutual Aid Public Welfare Foundation Artificial Liver Special Fund,No.iGandanF-1082024-RGG018the Student Innovation and Entrepreneurship Training Program of Zunyi Medical University,No.2024106610923.
文摘Metabolic dysfunction-associated steatotic liver disease,characterized by pathological intracellular triglyceride(TG)accumulation,is mechanistically associated with the disrupted spatiotemporal regulation of hepatocyte nuclear factor(HNF)-dependent transcriptional programs.HNFs,including key members such as HNF-1α,HNF-4α,and HNF-6,constitute a liver-enriched family of transcription factors that govern hepatic lipid metabolism through hierarchical transcriptional regulatory networks.These networks critically regulate the dynamic equilibrium of TG metabolism,encompassing TG synthesis,storage,lipolysis,and lipoprotein-mediated export.This review comprehensively deciphers the molecular cascades through which HNF dysfunction exacerbates TG metabolic disorder in metabolic dysfunction-associated steatotic liver disease.Additionally,we evaluate emerging translational strategies targeting key HNF regulatory nodes and discuss current clinical challenges as well as potential solutions.
基金supported by the National Natural Science Foundation of China(32241042)the National Key R&D Program of China(2019YFD1000700 and 2019YFD1000703)the Biological Breeding-National Science and Technology Major Project,China(2022ZD04017).
文摘Salt stress is a global constraint on agricultural production.Therefore,the development of salt tolerant plants has become a current research hotspot.While salt tolerance has evolved more frequently in C_(4) grass lineages,few studies have explored the molecular bases underlying salt stress tolerance in the C_(4) crop foxtail millet.In this study,we used a multi-pronged approach spanning the omics analyses of transcriptomes and physiological analysis of the C_(3) crop rice and the C_(4) model crop foxtail millet to investigate their responses to salt stress.The results revealed that compared to C_(3) rice,C_(4) foxtail millet has upregulated abscisic acid(ABA)and notably reduced CK biosynthesis and signaling transduction under salt stress.Salt stress in C_(3) rice plants triggered rapid downregulation of photosynthesis related genes,which was coupled with severely reduced net photosynthetic rates.In the salt-treated C_(3) rice and C_(4) foxtail millet,some stress responsive transcription factors(TFs),such as AP2/ERF,WRKY and MYB,underwent strong and distinct transcriptional changes.Based on a weighted gene co-expression network analysis(WGCNA),the AP2/ERF transcription factor Rice Starch Regulator1 SiRSR1(Seita.3G044600)was identified as a key regulator of the salt stress response.To confirm its function,we generated OsRSR1-knockout lines using CRISPR/Cas9 genome editing in rice and its upstream repressor SimiR172a-overexpressing(172a-OE)transgenic plants in foxtail millet,which both showed increased salt tolerance.Overall,this study not only provides new insights into the convergent regulation of the salt stress responses of foxtail millet and rice,but it also sheds light on the divergent signaling networks between them in response to salt stress.
基金supported in part by grants from the National Natural Science Foundation of China (81870397 to X.D.L.81620108002, 81771732, 81830016 to X.M+2 种基金and 81570469 to R.Q.T.)by grants from Jiangsu provincial research fund (BE2017713 to X.D.L and BL2018657 to Y.T.)a grant from National Key R&D Program of China (2016YFC0900400)。
文摘Primary biliary cholangitis(PBC) is an autoimmune disease involving dysregulation of a broad array of homeostatic and metabolic processes. Although considerable single-nucleotide polymorphisms have been unveiled, a large fraction of risk factors remains enigmatic. Candidate genes with rare mutations that tend to confer more deleterious effects need to be identified. To help pinpoint cellular and developmental mechanisms beyond common noncoding variants, we integrate whole exome sequencing with integrative network analysis to investigate genes harboring de novo mutations. Prominent convergence has been revealed on a network of disease-specific co-expression comprised of 55 genes associated with homeostasis and metabolism. The transcription factor gene MEF2 D and the DNA repair gene PARP2 are highlighted as hub genes and identified to be up-and down-regulated, respectively, in peripheral blood data set. Enrichment analysis demonstrates that altered expression of MEF2 D and PARP2 may trigger a series of molecular and cellular processes with pivotal roles in PBC pathophysiology. Our study identifies genes with de novo mutations in PBC and suggests that a subset of genes in homeostasis and metabolism tend to act in synergy through converging on co-expression network, providing novel insights into the etiology of PBC and expanding the pool of molecular candidates for discovering clinically actionable biomarkers.
基金This work was supported by grants from the National Key Research and Development Program of China(2018YFA0107804)the National Natural Science Foundation of China(81900117,82131430173)the CAMS Initiative for Innovative Medicine(2021-I2M-1–040).
文摘Highly heterogeneous acute myeloid leukemia(AML)exhibits dysregulated transcriptional programs.Transcription factor(TF)regulatory networks underlying AML subtypes have not been elucidated at single-cell resolution.Here,we comprehensively mapped malignancy-related TFs activated in different AML subtypes by analyzing single-cell RNA sequencing data from AMLs and healthy donors.We first identified six modules of regulatory networks which were prevalently dysregulated in all AML patients.AML subtypes featured with different malignant cellular composition possessed subtype-specific regulatory TFs associated with differentiation suppression or immune modulation.At last,we validated that ERF was crucial for the development of hematopoietic stem/progenitor cells by performing loss-and gain-of-function experiments in zebrafish embryos.Collectively,our work thoroughly documents an abnormal spectrum of transcriptional regulatory networks in AML and reveals subtype-specific dysregulation basis,which provides a prospective view to AML pathogenesis and potential targets for both diagnosis and therapy.
文摘Determining how cells regulate their transcriptional response toextracellular signals is key to the understanding of complex eukaryotic systems. This study wasinitiated with the goals of furthering the study of mammalian transcriptional regulation andanalyzing the relative benefits of related computational methodologies. One dataset available forsuch an analysis involved gene expression profiling of the early growth factor response to plateletderived growth factor (PDGF) in a human glioblastoma cell line; this study differentiated geneswhose expression was regulated by signaling through the phosphoinositide-3-kinase (PI3K) versus theextracellular-signal regulated kinase (ERK) pathways. We have compared the inferred transcriptionfactors from this previous study with additional predictions of regulatory transcription factorsusing two alternative promoter sequence analysis techniques. This comparative analysis, in which thealgorithms predict overlapping, although not identical, sets of factors, argues for meticulousbenchmarking of promoter sequence analysis methods to determine the positive and negative attributesthat contribute to their varying results. Finally, we inferred transcriptional regulatory networksderiving from various signaling pathways using the CARRIE program suite. These networks not onlyincluded previously described transcriptional features of the response to growth signals, but alsopredicted new regulatory features for the propagation and modulation of the growth signal.
基金This study was supported by the Research Network of Computational Biology and the Supercomputing Center at Beijing Institutes of Life Science,Chinese Academy of SciencesThis work was supported by the Strategic Priority Research Program of CAS(XDB11010200 and 11010100)and the National Natural Science Foundation of China(Grant Nos.31771452,31401121,and 31772531).
文摘Phenotypic plasticity plays fundamental roles in successful adaptation of animals in response to environmental variations.Here,to reveal the transcriptome reprogramming in locust phase change,a typical phenotypic plasticity,we conducted a comprehensive analysis of multiple phase-related transcriptomic datasets of the migratory locust.We defined PhaseCore genes according to their contribution to phase differentiation by the adjustment for confounding principal components analysis algorithm(AC-PCA).Compared with other genes,PhaseCore genes predicted phase status with over 87.5%accuracy and displayed more unique gene attributes including the faster evolution rate,higher CpG content and higher specific expression level.Then,we identified 20 transcription factors(TFs)named PhaseCoreTF genes that are associated with the regulation of PhaseCore genes.Finally,we experimentally verified the regulatory roles of three representative TFs(Hr4,Hr46,and grh)in phase change by RNAi.Our findings revealed that core transcriptional signatures are involved in the global regulation of locust phase changes,suggesting a potential common mechanism underlying phenotypic plasticity in insects.The expression and network data are accessible in an online resource called LocustMine(http://www.locustmine.org:8080/locustmine).
基金This work was supported by the National Key Research and Development Program of China(no.2016YFD0600106)We also acknowledge financial support from the National Natural Science Foundation of China(grant nos.32001332 and 32001331)+1 种基金the Fundamental Research Funds for the Central Universities of China(grant nos.2572018CL01 and 2572018CL02)the Heilongjiang Touyan Innovation Team Program(Tree Genetics and Breeding Innovation Team).
文摘Tension wood(TW)is a specialized xylem tissue formed in angiosperm trees under gravitational stimulus or mechanical stresses(e.g.,bending).The genetic regulation that underlies this important mechanism remains poorly understood.Here,we used laser capture microdissection of stem xylem cells coupled with full transcriptome RNA-sequencing to analyze TW formation in Populus trichocarpa.After tree bending,PtrLBD39 was the most significantly induced transcription factor gene;it has a phylogenetically paired homolog,PtrLBD22.CRISPR-based knockout of PtrLBD39/22 severely inhibited TW formation,reducing cellulose and increasing lignin content.Transcriptomic analyses of CRISPR-based PtrLBD39/22 double mutants showed that these two genes regulate a set of TW-related genes.Chromatin immunoprecipitation sequencing(ChIP-seq)was used to identify direct targets of PtrLBD39.We integrated transcriptomic analyses and ChIP-seq assays to construct a transcriptional regulatory network(TRN)mediated by PtrLBD39.In this TRN,PtrLBD39 directly regulates 26 novel TW-responsive transcription factor genes.Our work suggests that PtrLBD39 and PtrLBD22 specifically control TW formation by mediating a TW-specific TRN in Populus.
文摘Metabolism is regulated at multiple levels in response to the changes of internal or external conditions. Transcriptional regulation plays an important role in regulating many metabolic reactions by altering the concentrations of metabolic enzymes. Thus, integration of the transcriptional regulatory information is necessary to improve the accuracy and predictive ability of metabolic models. Here we review the strategies for the reconstruction of a transcriptional regulatory network （TRN） for yeast and the integration of such a reconstruction into a flux balance analysis-based metabolic model. While many large-scale TRN reconstructions have been reported for yeast, these reconstructions still need to be improved regarding the functionality and dynamic property of the regulatory interactions. In addition, mathematical modeling approaches need to be further developed to efficiently integrate transcriptional regulatory interactions to genome-scale metabolic models in a quantitative manner.
基金supported by grants from the National Natural Sciences Foundation of China(U22A20466 and 32472118)the Open Funds of the State Key Laboratory of Crop Genetics&Germplasm Enhancement and Utilization(ZW202403)+2 种基金China Postdoctoral Science Foundation(2023M741064)the Research Project of Science and Technology of Henan Province(242102111121)Innovation Team of Henan High Education(25IRTSTHN028).
文摘Because cereal kernel texture is a determinant of maize end-use properties,it is desirable to elucidate the genetic control of kernel formation and thereby to optimize maize kernel texture for breeding.Basically,maize kernel texture is determined by the ratio of vitreous endosperm in the peripheral region to the floury endosperm in the center of the kernel.In contrast to the puroindoline proteins(Pins)as the major determinants of grain texture specific to wheat,maize kernel texture is a quantitative trait that is controlled by many minor-effect genes.Nonetheless,substantial progresses have been made in unravelling gene regulatory networks underlying maize kernel formation that is related to its texture.Here,we review the current knowledge on maize endosperm development,focusing on vitreous and floury endosperm formation,and summarize the potential transcription regulatory mechanisms for starch and zein biosynthesis.The integration of the information will potentially provide valuable candidate genes for breeding maize varieties with improved kernel texture and quality.
基金supported by the China National Natural Sciences Foundation(32070314)to J.X.
文摘Nickel(Ni),a component of urease,is a micronutrient essential for plant growth and development,but excess Ni is toxic to plants.Tomato(Solanum lycopersicum L.)is one of the important vegetables worldwide.Excessive use of fertilizers and pesticides led to Ni contamination in agricultural soils,thus reducing yield and quality of tomatoes.However,the molecular regulatory mechanisms of Ni toxicity responses in tomato plants have largely not been elucidated.Here,we investigated the molecular mechanisms underlying the Ni toxicity response in tomato plants by physiobiochemical,transcriptomic and molecular regulatory network analyses.Ni toxicity repressed photosynthesis,induced the formation of brush-like lateral roots and interfered with micronutrient accumulation in tomato seedlings.Ni toxicity also induced reactive oxygen species accumulation and oxidative stress responses in plants.Furthermore,Ni toxicity reduced the phytohormone concentrations,including auxin,cytokinin and gibberellic acid,thereby retarding plant growth.Transcriptome analysis revealed that Ni toxicity altered the expression of genes involved in carbon/nitrogen metabolism pathways.Taken together,these results provide a theoretical basis for identifying key genes that could reduce excess Ni accumulation in tomato plants and are helpful for ensuring food safety and sustainable agricultural development.
基金Supported by National Institute of Health Grant GM47475, Department of Energy Grant DE-FG03-87ER13742, and U.S. Department of Agriculture Grant 5335-21000-010-00D. Publication of this paper is supported by the National Natural Science Foundation of China （30624808） and Science Publication Foundation of the Chinese Academy of Sciences.Acknowledgements Thank the coauthors of the original research publications used as the basis for this article, and Jim Tepperman for figure preparation and help with the manuscript.
文摘Identification of all genes involved in the phytochrome （phy）-medieted responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth end development. This article highlights end integrates the central findings of two recent comprehensive studies in Arabidopsis that have identified the genome-wide set of phy-reguleted genes that respond rapidly to red-light signals upon first exposure of dark-grown seedlings, and have tested the functional relevance to normal seedling photomorphogenesis of an Initial subset of these genes. The data： （a） reveal considerable complexity in the channeling of the light signals through the different phy-femily members （phyA to phyE） to responsive genes; （b） identify a diversity of transcription-factor-encoding genes as major early, if not primary, targets of phy signaling, end, therefore, as potentially important regulators in the transcriptional-network hierarchy; and （c） identify auxin-related genes as the dominant class among rapidly-regulated, hormone-related genes. However, reverse-genetic functional profiling of a selected subset of these genes reveals that only a limited fraction are necessary for optimal phy-induced seedling deetioletion.
文摘During the floral transition the shoot apical meristem changes its identity from a vegetative to an inflorescence state. This change in identity can be promoted by external signals, such as inductive photoperiod conditions or vernalization, and is accompanied by changes in expression of key developmental genes. The change in meristem identity is usually not reversible, even if the inductive signal occurs only transiently. This implies that at least some of the key genes must possess an intrinsic memory of the newly acquired expression state that ensures irreversibility of the process. In this review, we discuss different molecular scenarios that may underlie a molecular memory of gene expression.
基金the European Commission’s Directorate General for Research within the 7th Framework Program(FP7/2007–2013)under Grant Agreement 270089(MULTIBIOPRO to ARF and SP)
文摘The construction of a secondary cell wall is an important and necessary developmental decision that sup- ports cell function and plant stature. Unlike the primary cell walls, which are initiated during cell division and develop along with the expansion of the cells, secondary cell walls are constructed after the cells have stopped growing. Hence, the transition from primary to secondary wall synthesis marks an important and distinct metabolic investment by the plant. This transition requires a coordi- nated change of a plethora of cellular processes, including hormonal, transcriptional and post-transcriptional activi- ties, metabolic flux re-distributions and enzymatic activities. In this review, we briefly summarize the hormonal and transcriptional control of the primary to secondary wall transition, and highlight important gaps in our under- standing of the metabolic framework that support the transition. Several tools that may aid in future research efforts to better understand the changes in cell wall synthesis during the trans-differentiation are also discussed.
基金supported by the National Natural Science Foundation of China(grants 91935305 and 31730065 to R.S.).
文摘Recent breakthroughs in transcriptome analysis and gene characterization have provided valuable resources and information about the maize endosperm developmental program.The high temporal-resolution transcriptome analysis has yielded unprecedented access to information about the genetic control of seed development.Detailed spatial transcriptome analysis using laser-capture microdissection has revealed the expression patterns of specific populations of genes in the four major endosperm compartments:the basal endosperm transfer layer(BETL),aleurone layer(AL),starchy endosperm(SE),and embryo-surrounding region(ESR).Although the overall picture of the transcriptional regulatory network of endosperm development remains fragmentary,there have been some exciting advances,such as the identification of OPAQUE11(O11)as a central hub of the maize endosperm regulatory network connecting endosperm development,nutrient metabolism,and stress responses,and the discovery that the endosperm adjacent to scutellum(EAS)serves as a dynamic interface for endosperm-embryo crosstalk.In addition,several genes that function in BETL development,AL differentiation,and the endosperm cell cycle have been identified,such as ZmSWEET4c,Thk1,and Dek15,respectively.Here,we focus on current advances in understanding the molecular factors involved in BETL,AL,SE,ESR,and EAS development,including the specific transcriptional regulatory networks that function in each compartment during endosperm development.
文摘Lineage commitment of thymocytes can be distinguished and modulated by key factors of transcriptional networks,such as the antagonistic expression and function of Th-POK and Runx3 in the CD4 and CD8 lineages1 and Foxp32 and PLZF3 in CD4^(+)regulatory T(Treg)cells and natural killer T(NKT)cells,respectively.
