N^(6)-methyladenine(6mA)is a prevalent DNA modification and is involved in a wide range of human diseases.Previous studies have indicated that 6mA is enriched in mitochondrial DNA(mtDNA)of mammals.By employing an evol...N^(6)-methyladenine(6mA)is a prevalent DNA modification and is involved in a wide range of human diseases.Previous studies have indicated that 6mA is enriched in mitochondrial DNA(mtDNA)of mammals.By employing an evolved adenine deaminase,we developed a deaminase-mediated sequencing(DM-seq)method that could achieve genome-wide mapping of 6mA in mammalian mtDNA at single-base resolution.In this study,we used an engineered adenine deaminase,known as TadA8e protein,to map 6mA in mtDNA of hepatocellular carcinoma(HCC)by DM-seq.Through high-throughput sequencing,we identified sixteen 6mA sites in both HCC and adjacent normal tissue mtDNA.The results revealed an increased overall 6mA level in mtDNA associated with HCC.Furthermore,an elevation in 6mA level was observed alongside a decrease in the m RNA levels of the corresponding genes,indicating that increased6mA level hindered transcription processes related to these genes.These findings demonstrate that 6mA in mtDNA is correlated with HCC and provide evidence supporting the inhibitory effect of elevated 6mA level on subsequent transcriptional activity.This research illuminates the intricate relationship between 6mA modification and transcriptional regulation in the context of HCC,offering valuable insights into the role of 6mA modification in HCC pathogenesis.展开更多
Differences between healthy subjects and associated disease risks are of substantial interest in clinical medicine. Based on clinical presentations, Traditional Chinese Medicine （TCM） classifies healthy people into ...Differences between healthy subjects and associated disease risks are of substantial interest in clinical medicine. Based on clinical presentations, Traditional Chinese Medicine （TCM） classifies healthy people into nine constitutions： Balanced, Qi, Yang or Yin deficiency, Phlegm-dampness, Damp-heat, Blood stasis, Qi stagnation, and Inherited special constitutions. In particular, Yang and Yin deficiency constitutions exhibit cold and heat aversion, respectively. However, the intrinsic molecular characteristics of unbal- anced phenotypes remain unclear. To determine whether gene expression-based clustering can reca- pitulate TCM-based classification, peripheral blood mononudear cells （PBMCs） were collected from Chinese Han individuals with Yang/Yin deficiency （n = 12 each） and Balanced （n = 8） constitutions, and global gene expression profiles were determined using the Affymetrix HC-UI33A Plus 2.0 array. Notably, we found that gene expression-based classifications reflected distinct TCM-based subtypes. Consistent with the clinical observation that subjects with Yang deficiency tend toward obesity, series-clustering analysis detected several key lipid metabolic genes （diacylglycerol acyltransferase （DGAT2）, acyl-CoA synthetase （ACSL1）, and ATP-hinding cassette subfamily A member 1 （ABCAI）） to be down- and up- regulated in Yin and Yang deficiency constitutions, respectively. Our findings suggest that Yin]Yang deficiency and Balanced constitutions are unique entities in their mRNA expression profiles. Moreover, the distinct physical and clinical characteristics of each unbalanced constitution can be explained, in part, by specific gene expression signatures.展开更多
Translesion DNA synthesis(TLS)can bypass DNA lesions caused by chemotherapeutic drugs,which usually result in drug resistance.Given its key role in mutagenesis and cell survival after DNA damage,inhibition of the TLS ...Translesion DNA synthesis(TLS)can bypass DNA lesions caused by chemotherapeutic drugs,which usually result in drug resistance.Given its key role in mutagenesis and cell survival after DNA damage,inhibition of the TLS pathway has emerged as a potential target for improving the efficacy of DNA-damaging agents such as cisplatin(CDDP),a widely used anticancer agent.Unfortunately,few suitable natural TLS inhibitors have been reported.Here,we found that a triterpenoid compound Ganoboninketal C(26-3)from Ganoderma boninense,a traditional Chinese medicine,can impair CDDP-induced TLS polymerase eta(Polη)focus formation,PCNA monoubiquitination as well as mutagenesis.Moreover,26-3 can significantly sensitize tumor cells to CDDP killing and reduce the proportion of cancer stem cells in AGS and promote apoptosis after CDDP exposure.Interestingly,26-3 can also sensitize tumor cells to Gefitinib therapy.Mechanistically,through RNA-seq analysis,we found that 26-3 could abrogate the CDDP-induced upregulation of Polηand PIDD(p53-induced protein with a death domain),2 known factors promoting TLS pathway.Furthermore,we found that activating transcription factor 3 is a potential novel TLS modulator.Taken together,we have identified a natural TLS inhibitor 26-3,which can be potentially used as an adjuvant to improve clinical efficacy.展开更多
Artificial selection during domestication and post-domestication improvement results in loss of genetic diversity near target loci. However, the genetic locus associated with cob glume color and the nature of the geno...Artificial selection during domestication and post-domestication improvement results in loss of genetic diversity near target loci. However, the genetic locus associated with cob glume color and the nature of the genomic pattern surrounding it was elusive and the selection effect in that region was not clear. An association mapping panel consisting of 283 diverse modern temperate maize elite lines was genotyped by a chip containing over 55,000 evenly distributed SNPs. Ten-fold resequencing at the target region on 40 of the panel lines and 47 tropical lines was also undertaken. A genome-wide association study(GWAS) for cob glume color confirmed the P1 locus, which is located on the short arm of chromosome 1, with a-log10 P value for surrounding SNPs higher than the Bonferroni threshold(α/n, α < 0.001) when a mixed linear model(MLM) was implemented. A total of 26 markers were identified in a 0.78 Mb region surrounding the P1 locus, including 0.73 Mb and 0.05 Mb upstream and downstream of the P1 gene, respectively. A clear linkage disequilibrium(LD) block was found and LD decayed very rapidly with increasing physical distance surrounding the P1 locus. The estimates of π and Tajima's D were significantly(P < 0.001) lower at both ends compared to the locus. Upon comparison of temperate and tropical lines at much finer resolution by resequencing(180-fold finer than chip SNPs), a more structured LD block pattern was found among the 40 resequenced temperate lines. All evidence indicates that the P1 locus in temperate maize has not undergone neutral evolution but has been subjected to artificial selection during post-domestication selection or improvement. The information and analytical results generated in this study provide insights as to how breeding efforts have affected genome evolution in crop plants.展开更多
Background:Bladder cancer is a common malignancy of the genitourinary system.Recent studies have confirmed the existence of microorganisms in urine.This study aimed to characterize changes in the urinary microbiota of...Background:Bladder cancer is a common malignancy of the genitourinary system.Recent studies have confirmed the existence of microorganisms in urine.This study aimed to characterize changes in the urinary microbiota of Chinese bladder cancer patients and determine differences between patients with muscle-invasive bladder cancer(MIBC)and those with non-muscle-invasive bladder cancer(NMIBC).Methods:Urine samples were collected from 64 patients with bladder cancer and 94 disease-free controls using the clean catch method and sequenced by 16S rRNA gene sequencing.Sequencing reads were filtered by VSEARCH and clustered by UPARSE.Results:Significant associations were found between urinary microbiota and factors such as sex,age,and disease status.After age adjustment,differences in beta diversity were observed between healthy men and women,cancer patients and healthy controls,and NMIBC and MIBC patients.The cancer patients had an increased abundance of 14 bacterial genera,including Stenotrophomonas,Propionibacterium,and Acinetobacter.Notably,Peptoniphilus spp.were enriched in high-risk MIBC patients,indicating their potential as a risk marker.Functional prediction via PICRUSt analysis suggested enriched metabolic pathways in specific disease groups.Furthermore,molecular ecological network analysis revealed differences based on sex and disease type.Conclusions:This significant microbial diversity indicates a potential correlation between urinary microbiota dysbiosis and bladder cancer,with implications for risk stratification and disease management.The identified urinary microbiota may serve as noninvasive markers for bladder cancer,warranting further validation in larger cohorts.This study provides a foundation for further research on the mechanisms of bladder cancer progression.展开更多
Drought severely threatens food security, and its detrimental effects will be exacerbated by climate change in many parts of the world. Rice production is water-consuming and particularly vulnerable to drought stress....Drought severely threatens food security, and its detrimental effects will be exacerbated by climate change in many parts of the world. Rice production is water-consuming and particularly vulnerable to drought stress. Upland rice is a special rice ecotype that specifically adapts to dryland mainly due to its robust root system. However, the molecular and developmental mechanism underlying this adaption has remained elusive. In this study, by comparing the root development between upland and irrigated rice phenotypically and cytologically, we identified key developmental phenotypes that distinguish upland rice from irrigated rice. We further generated spatial transcriptomic atlases for coleoptilar nodes and root tips to explore their molecular differences in crown root formation and development, uncovering promising genes for enhancing rice drought resistance. Among the identified genes, HMGB1, a transcriptional regulator, functions as a key factor that facilitates root elongation and thickening in upland rice and thereby enhances drought resistance. In summary, our study uncovers spatially resolved transcriptomic features in roots of upland rice that contribute to its adaptation to dryland conditions, providing valuable genetic resources for breeding drought-resilient rice.展开更多
As some of the earliest evolving flowering plants,waterlilies offer unique insights into angiosperm evolu-tion.Giant Amazonian waterlilies(genus Victoria)are of particular interest due to their production of the world...As some of the earliest evolving flowering plants,waterlilies offer unique insights into angiosperm evolu-tion.Giant Amazonian waterlilies(genus Victoria)are of particular interest due to their production of the world’s largest floating leaves and gigantic flowers that entrap pollinating beetles.Here,we report chromo-some-level genome assemblies of Victoria cruziana and three related waterlilies:Euryale ferox,Nymphaea mexicana,and Brasenia schreberi.We found an ancient whole-genome duplication event specific to the Nymphaeales.We reveal major gene duplication and loss events throughout the evolution of angiosperms,with substantial implications for flower development and the biosynthesis of floral volatile organic com-pounds(FVOCs)in waterlilies.Importantly,we report a unique division of labor in the stamen function of V.cruziana linked to beetle attraction by FVOCs.This is related to the ultra-high expression of VicSABATHa along with Vicchitinase,possibly linked to protection from damage by trapped beetles.Overexpression of VicSABATHa in tobacco leaves reveals a capacity to produce volatile fatty acids,confirming its role in their catalytic synthesis.Overall,these findings provide novel insights into the evolution and adaptations of waterlilies and flowering plants in general.展开更多
Uncovering the functionally essential variations related to tumorigenesis and tumor progression from cancer genomics data is still challenging due to the genetic diversity among patients,and extensive inter-and intra-...Uncovering the functionally essential variations related to tumorigenesis and tumor progression from cancer genomics data is still challenging due to the genetic diversity among patients,and extensive inter-and intra-tumoral heterogeneity at different levels of gene expression regulation,including but not limited to the genomic,epigenomic,and transcriptional levels.To minimize the impact of germline genetic heterogeneities,in this study,we establish multiple primary cultures from the primary and recurrent tumors of a single patient with hepatocellular carcinoma(HCC).Multiomics sequencing was performed for these cultures that encompass the diversity of tumor cells from the same patient.Variations in the genome sequence,epigenetic modification,and gene expression are used to infer the phylogenetic relationships of these cell cultures.We find the discrepancy among the relationships revealed by single nucleotide variations(SNVs)and transcriptional/epigenomic profiles from the cell cultures.We fail to find overlap between sample-specific mutated genes and differentially expressed genes(DEGs),suggesting that most of the heterogeneous SNVs among tumor stages or lineages of the patient are functionally insignificant.Moreover,copy number alterations(CNAs)and DNA methylation variation within gene bodies,rather than promoters,are significantly correlated with gene expression variability among these cell cultures.Pathway analysis of CNA/DNA methylation-related genes indicates that a single cell clone from the recurrent tumor exhibits distinct cellular characteristics and tumorigenicity,and such an observation is further confirmed by cellular experiments both in vitro and in vivo.Our systematic analysis reveals that CNAs and epigenomic changes,rather than SNVs,are more likely to contribute to the phenotypic diversity among subpopulations in the tumor.These findings suggest that new therapeutic strategies targeting gene dosage and epigenetic modification should be considered in personalized cancer medicine.This culture model may be applied to the further identification of plausible determinants of cancer metastasis and relapse.展开更多
Within the past 10 years, the progress of genomics development in China exhibited a frogleap in terms of scale, quality, organization, and international collaboration. Human genome study has entered a new phase of int...Within the past 10 years, the progress of genomics development in China exhibited a frogleap in terms of scale, quality, organization, and international collaboration. Human genome study has entered a new phase of interdisciplinarity in the history of life science in China. The rise of genomics relied on the development of technology and its integration with other academic disciplines, particularly in the following three areas. First, DNA sequencing technology has been improving its productivity and efficiency at an exponential growth rate. Second, bioinformatics supports the system of data collection, administration, annotation,展开更多
Micronutrient deficiencies affect more than two billion people worldwide,resulting in poor health,developmental issues,and even death.Iron deficiency is one of the most prevalent micronutrient deficiencies worldwide a...Micronutrient deficiencies affect more than two billion people worldwide,resulting in poor health,developmental issues,and even death.Iron deficiency is one of the most prevalent micronutrient deficiencies worldwide and impacts approximately one-third of the global population.It can lead to anemia,fatigue.展开更多
The colorful,nutrient-rich peels of citrus fruits have long been valued for their tangy flavors and aromatic oils.These oils are produced and stored in special secretory structures called oil glands,which are prevalen...The colorful,nutrient-rich peels of citrus fruits have long been valued for their tangy flavors and aromatic oils.These oils are produced and stored in special secretory structures called oil glands,which are prevalent across citrus varieties(Knight et al.,2001).Oil glands serve as"reservoirs"for diverse metabolites such as terpenes and flavonoids that give citrus fruits their characteristic aroma(Mahato et al.,2019;Voo et al.,2012;Xian et al.,2022).Many of these compounds also act as chemical defenses against pest and pathogens(Fisher and Phillips,2008).展开更多
Exosomes are 40–100 nm nano-sized vesicles that are released from many cell types into the extracellular space. Such vesicles are widely distributed in various body fluids. Recently,m RNAs and micro RNAs（mi RNAs） h...Exosomes are 40–100 nm nano-sized vesicles that are released from many cell types into the extracellular space. Such vesicles are widely distributed in various body fluids. Recently,m RNAs and micro RNAs（mi RNAs） have been identified in exosomes, which can be taken up by neighboring or distant cells and subsequently modulate recipient cells. This suggests an active sorting mechanism of exosomal mi RNAs, since the mi RNA profiles of exosomes may differ from those of the parent cells. Exosomal mi RNAs play an important role in disease progression, and can stimulate angiogenesis and facilitate metastasis in cancers. In this review, we will introduce the origin and the trafficking of exosomes between cells, display current research on the sorting mechanism of exosomal mi RNAs, and briefly describe how exosomes and their mi RNAs function in recipient cells.Finally, we will discuss the potential applications of these mi RNA-containing vesicles in clinical settings.展开更多
Dear Editor,Aging is the leading risk factor for many chronic diseases,accounting for almost 60%of all deaths worldwide.How to achieve healthy aging,alleviate aging-related diseases,and extend healthspan has become a ...Dear Editor,Aging is the leading risk factor for many chronic diseases,accounting for almost 60%of all deaths worldwide.How to achieve healthy aging,alleviate aging-related diseases,and extend healthspan has become a main topic of biomedical research(He et al.,2019).Geroprotective compounds,such as metformin and rapamycin,have been shown to improve both healthspan and lifespan in mice(Martin-Montalvo et al.,2013;Bitto et al.,2016),whereas nicotinamide partially improves healthspan in mice(Mitchell et al.,2018).展开更多
N^(6)-methyladenosine(m^(6)A)is the most abundant modification observed in eukaryotic mRNAs.Advances in transcriptome-wide m^(6)A mapping and sequencing technologies have enabled the identification of several conserve...N^(6)-methyladenosine(m^(6)A)is the most abundant modification observed in eukaryotic mRNAs.Advances in transcriptome-wide m^(6)A mapping and sequencing technologies have enabled the identification of several conserved motifs in plants,including the RRACH(R=A/G and H=A/C/U)and UGUAW(W=U or A)motifs.However,the mechanisms underlying deposition of m^(6)A marks at specific positions in the conserved motifs of individual transcripts remain to be clarified.Evidence from plant and animal studies suggests that m^(6)A writer or eraser components are recruited to specific genomic loci through interactions with particular transcription factors,5-methylcytosine DNA methylation marks,and histone marks.In addition,recent studies in animal cells have shown that microRNAs play a role in depositing m^(6)A marks at specific sites in transcripts through a base-pairing mechanism.m^(6)A also affects the biogenesis and function of chromatin-associated regulatory RNAs and long noncoding RNAs.Although we have less of an understanding of the link between m^(6)A modification and epigenetic factors in plants than in animals,recent progress in identifying the proteins that interact with m^(6)A writer or eraser components has provided insights into the crosstalk between m^(6)A modification and epigenetic factors,which plays a crucial role in transcript-specific methylation and regulation of m^(6)A in plants.展开更多
PINK1/Parkin-mediated mitophagy is an important process in selective removal of damaged mitochondria, in which translocation of Parkin to damaged mitochondria is recognized as an initiation step. At present, how the d...PINK1/Parkin-mediated mitophagy is an important process in selective removal of damaged mitochondria, in which translocation of Parkin to damaged mitochondria is recognized as an initiation step. At present, how the damaged mitochondria are selectively recognized and targeted by Parkin is not fully understood. Here we show that Miro2, an outer mitochondrial membrane protein, undergoes demultimerization from a tetramer to a monomer and alteration in mitochondrial localization upon CCCP treatment, suggesting a CCCP-induced realignment of Miro2. The realignment of Miro2 is tightly regulated by PINK1-mediated phosphorylation at Ser325/Ser430 and by Ca^2+binding to EF2 domain, which are both essential for the subsequent Parkin translocation. Interestingly, ablation of Miro2 in mouse causes delayed reticulocyte maturation, lactic acidosis and cardiac disorders. Furthermore, several Miro2 mutations found in the congenital lactic acidosis patients also disable its realignment and Parkin translocation. These findings reveal an important role of Miro2 to mediate Parkin translocation by sensing both depolarization and Ca^2+release from damaged mitochondria to ensure the accuracy of mitophagy.展开更多
T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus(CMV)infection1 and the ongoing COVID-19 pandemic caused by SARS-Co...T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus(CMV)infection1 and the ongoing COVID-19 pandemic caused by SARS-CoV-2.^(2) CMV-related diseases occur once the host immune system is impaired or lacks a protective repertoire of virus-specific T lymphocytes.3 Adoptive transfer of T-cell receptor(TCR)-engineered T cells(TCR-Ts)provides an encouraging alternative treatment option for patients with CMV reactivation.^(4) However,generating TCR-Ts requires the identification of epitope-specific and functional TCR pairs.Modern single-cell sequencing techniques open up the ability to unravel TCR repertoires,^(5 )which offers a potential opportunity to screen functional TCR pairs for TCR-T therapy.Here,we report an efficient approach that combines ex vivo CD8+T-cell stimulation with single-cell RNA and TCR V(D)J sequencing to identify CMV-specific TCRs for generating TCR-Ts.展开更多
基金supported by the National Natural Science Foundation of China(No.22277093)the Key Research and Development Project of Hubei Province(No.2023BCB094)。
文摘N^(6)-methyladenine(6mA)is a prevalent DNA modification and is involved in a wide range of human diseases.Previous studies have indicated that 6mA is enriched in mitochondrial DNA(mtDNA)of mammals.By employing an evolved adenine deaminase,we developed a deaminase-mediated sequencing(DM-seq)method that could achieve genome-wide mapping of 6mA in mammalian mtDNA at single-base resolution.In this study,we used an engineered adenine deaminase,known as TadA8e protein,to map 6mA in mtDNA of hepatocellular carcinoma(HCC)by DM-seq.Through high-throughput sequencing,we identified sixteen 6mA sites in both HCC and adjacent normal tissue mtDNA.The results revealed an increased overall 6mA level in mtDNA associated with HCC.Furthermore,an elevation in 6mA level was observed alongside a decrease in the m RNA levels of the corresponding genes,indicating that increased6mA level hindered transcription processes related to these genes.These findings demonstrate that 6mA in mtDNA is correlated with HCC and provide evidence supporting the inhibitory effect of elevated 6mA level on subsequent transcriptional activity.This research illuminates the intricate relationship between 6mA modification and transcriptional regulation in the context of HCC,offering valuable insights into the role of 6mA modification in HCC pathogenesis.
基金supported by the National Key Basic Research Program of China (973 Program No. 2011CB505400)
文摘Differences between healthy subjects and associated disease risks are of substantial interest in clinical medicine. Based on clinical presentations, Traditional Chinese Medicine （TCM） classifies healthy people into nine constitutions： Balanced, Qi, Yang or Yin deficiency, Phlegm-dampness, Damp-heat, Blood stasis, Qi stagnation, and Inherited special constitutions. In particular, Yang and Yin deficiency constitutions exhibit cold and heat aversion, respectively. However, the intrinsic molecular characteristics of unbal- anced phenotypes remain unclear. To determine whether gene expression-based clustering can reca- pitulate TCM-based classification, peripheral blood mononudear cells （PBMCs） were collected from Chinese Han individuals with Yang/Yin deficiency （n = 12 each） and Balanced （n = 8） constitutions, and global gene expression profiles were determined using the Affymetrix HC-UI33A Plus 2.0 array. Notably, we found that gene expression-based classifications reflected distinct TCM-based subtypes. Consistent with the clinical observation that subjects with Yang deficiency tend toward obesity, series-clustering analysis detected several key lipid metabolic genes （diacylglycerol acyltransferase （DGAT2）, acyl-CoA synthetase （ACSL1）, and ATP-hinding cassette subfamily A member 1 （ABCAI）） to be down- and up- regulated in Yin and Yang deficiency constitutions, respectively. Our findings suggest that Yin]Yang deficiency and Balanced constitutions are unique entities in their mRNA expression profiles. Moreover, the distinct physical and clinical characteristics of each unbalanced constitution can be explained, in part, by specific gene expression signatures.
基金supported by National Key Research and Development Program of China(2018YFA0108500)NSFC82341006,81673334,31970740,31801144,31800684 and 31701227+3 种基金Natural Science Foundation of Beijing(IS23071)Postdoctoral Research Foundation of China(2021M703206)Natural Science Foundation of Shanxi Province(202203021211155)the State Key Laboratory of Membrane Biology.
文摘Translesion DNA synthesis(TLS)can bypass DNA lesions caused by chemotherapeutic drugs,which usually result in drug resistance.Given its key role in mutagenesis and cell survival after DNA damage,inhibition of the TLS pathway has emerged as a potential target for improving the efficacy of DNA-damaging agents such as cisplatin(CDDP),a widely used anticancer agent.Unfortunately,few suitable natural TLS inhibitors have been reported.Here,we found that a triterpenoid compound Ganoboninketal C(26-3)from Ganoderma boninense,a traditional Chinese medicine,can impair CDDP-induced TLS polymerase eta(Polη)focus formation,PCNA monoubiquitination as well as mutagenesis.Moreover,26-3 can significantly sensitize tumor cells to CDDP killing and reduce the proportion of cancer stem cells in AGS and promote apoptosis after CDDP exposure.Interestingly,26-3 can also sensitize tumor cells to Gefitinib therapy.Mechanistically,through RNA-seq analysis,we found that 26-3 could abrogate the CDDP-induced upregulation of Polηand PIDD(p53-induced protein with a death domain),2 known factors promoting TLS pathway.Furthermore,we found that activating transcription factor 3 is a potential novel TLS modulator.Taken together,we have identified a natural TLS inhibitor 26-3,which can be potentially used as an adjuvant to improve clinical efficacy.
基金supported by the Chinese National "863" Program from the China Ministry of Science and Technology (Grant No. 2012AA10A306-3)the National Science Foundation of China (Grant No. 31171562) to CXthe Core Research Budget of the Non-profit Governmental Research Institution from the Chinese Government to the Institute of Crop Science, Chinese Academy of Agricultural Sciences (Grant No. 2012001)
文摘Artificial selection during domestication and post-domestication improvement results in loss of genetic diversity near target loci. However, the genetic locus associated with cob glume color and the nature of the genomic pattern surrounding it was elusive and the selection effect in that region was not clear. An association mapping panel consisting of 283 diverse modern temperate maize elite lines was genotyped by a chip containing over 55,000 evenly distributed SNPs. Ten-fold resequencing at the target region on 40 of the panel lines and 47 tropical lines was also undertaken. A genome-wide association study(GWAS) for cob glume color confirmed the P1 locus, which is located on the short arm of chromosome 1, with a-log10 P value for surrounding SNPs higher than the Bonferroni threshold(α/n, α < 0.001) when a mixed linear model(MLM) was implemented. A total of 26 markers were identified in a 0.78 Mb region surrounding the P1 locus, including 0.73 Mb and 0.05 Mb upstream and downstream of the P1 gene, respectively. A clear linkage disequilibrium(LD) block was found and LD decayed very rapidly with increasing physical distance surrounding the P1 locus. The estimates of π and Tajima's D were significantly(P < 0.001) lower at both ends compared to the locus. Upon comparison of temperate and tropical lines at much finer resolution by resequencing(180-fold finer than chip SNPs), a more structured LD block pattern was found among the 40 resequenced temperate lines. All evidence indicates that the P1 locus in temperate maize has not undergone neutral evolution but has been subjected to artificial selection during post-domestication selection or improvement. The information and analytical results generated in this study provide insights as to how breeding efforts have affected genome evolution in crop plants.
基金supported by the Guangdong Provincial Key Laboratory of Human Disease Genomics(Grant 2020B1212070028).
文摘Background:Bladder cancer is a common malignancy of the genitourinary system.Recent studies have confirmed the existence of microorganisms in urine.This study aimed to characterize changes in the urinary microbiota of Chinese bladder cancer patients and determine differences between patients with muscle-invasive bladder cancer(MIBC)and those with non-muscle-invasive bladder cancer(NMIBC).Methods:Urine samples were collected from 64 patients with bladder cancer and 94 disease-free controls using the clean catch method and sequenced by 16S rRNA gene sequencing.Sequencing reads were filtered by VSEARCH and clustered by UPARSE.Results:Significant associations were found between urinary microbiota and factors such as sex,age,and disease status.After age adjustment,differences in beta diversity were observed between healthy men and women,cancer patients and healthy controls,and NMIBC and MIBC patients.The cancer patients had an increased abundance of 14 bacterial genera,including Stenotrophomonas,Propionibacterium,and Acinetobacter.Notably,Peptoniphilus spp.were enriched in high-risk MIBC patients,indicating their potential as a risk marker.Functional prediction via PICRUSt analysis suggested enriched metabolic pathways in specific disease groups.Furthermore,molecular ecological network analysis revealed differences based on sex and disease type.Conclusions:This significant microbial diversity indicates a potential correlation between urinary microbiota dysbiosis and bladder cancer,with implications for risk stratification and disease management.The identified urinary microbiota may serve as noninvasive markers for bladder cancer,warranting further validation in larger cohorts.This study provides a foundation for further research on the mechanisms of bladder cancer progression.
基金supported by Biological Breeding-National Scinece and Tecnology Major Project(2023ZD04073)the National Natural Science Foundation of China(32070563 and 32470307)+3 种基金the Shenzhen Science and Technology Program(KQTD20230301092839007,KJZD20230921114607016)the Guangdong Laboratory of Lingnan Morden Agriculture(AGIS-ZDXM202203)the Fundamental Research Funds for the Central Universities(2662023SKPY002)Guangdong Provincial Key Laboratory of core collection of crop genetic resources research and application,BGl-Shenzhen,Shenzhen 518120,China(NO.2011A091000047).
文摘Drought severely threatens food security, and its detrimental effects will be exacerbated by climate change in many parts of the world. Rice production is water-consuming and particularly vulnerable to drought stress. Upland rice is a special rice ecotype that specifically adapts to dryland mainly due to its robust root system. However, the molecular and developmental mechanism underlying this adaption has remained elusive. In this study, by comparing the root development between upland and irrigated rice phenotypically and cytologically, we identified key developmental phenotypes that distinguish upland rice from irrigated rice. We further generated spatial transcriptomic atlases for coleoptilar nodes and root tips to explore their molecular differences in crown root formation and development, uncovering promising genes for enhancing rice drought resistance. Among the identified genes, HMGB1, a transcriptional regulator, functions as a key factor that facilitates root elongation and thickening in upland rice and thereby enhances drought resistance. In summary, our study uncovers spatially resolved transcriptomic features in roots of upland rice that contribute to its adaptation to dryland conditions, providing valuable genetic resources for breeding drought-resilient rice.
基金supported by the National Natural Science Foundation of China(32272750 and 31970246)the Scientific and Technological Talents and Platform Program of Yunnan Province(Academician Expert Workstation,202305AF150165)the"Pioneer"and"Leading Goose"R&D Program of Zhejiang(2023C02028).
文摘As some of the earliest evolving flowering plants,waterlilies offer unique insights into angiosperm evolu-tion.Giant Amazonian waterlilies(genus Victoria)are of particular interest due to their production of the world’s largest floating leaves and gigantic flowers that entrap pollinating beetles.Here,we report chromo-some-level genome assemblies of Victoria cruziana and three related waterlilies:Euryale ferox,Nymphaea mexicana,and Brasenia schreberi.We found an ancient whole-genome duplication event specific to the Nymphaeales.We reveal major gene duplication and loss events throughout the evolution of angiosperms,with substantial implications for flower development and the biosynthesis of floral volatile organic com-pounds(FVOCs)in waterlilies.Importantly,we report a unique division of labor in the stamen function of V.cruziana linked to beetle attraction by FVOCs.This is related to the ultra-high expression of VicSABATHa along with Vicchitinase,possibly linked to protection from damage by trapped beetles.Overexpression of VicSABATHa in tobacco leaves reveals a capacity to produce volatile fatty acids,confirming its role in their catalytic synthesis.Overall,these findings provide novel insights into the evolution and adaptations of waterlilies and flowering plants in general.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB13000000)the National Natural Science Foundation of China(Grant Nos.91531305,31771416,81373422,31301036,and 31801094)National Key Basic Research Program of China(Grant No.2014CB542006).
文摘Uncovering the functionally essential variations related to tumorigenesis and tumor progression from cancer genomics data is still challenging due to the genetic diversity among patients,and extensive inter-and intra-tumoral heterogeneity at different levels of gene expression regulation,including but not limited to the genomic,epigenomic,and transcriptional levels.To minimize the impact of germline genetic heterogeneities,in this study,we establish multiple primary cultures from the primary and recurrent tumors of a single patient with hepatocellular carcinoma(HCC).Multiomics sequencing was performed for these cultures that encompass the diversity of tumor cells from the same patient.Variations in the genome sequence,epigenetic modification,and gene expression are used to infer the phylogenetic relationships of these cell cultures.We find the discrepancy among the relationships revealed by single nucleotide variations(SNVs)and transcriptional/epigenomic profiles from the cell cultures.We fail to find overlap between sample-specific mutated genes and differentially expressed genes(DEGs),suggesting that most of the heterogeneous SNVs among tumor stages or lineages of the patient are functionally insignificant.Moreover,copy number alterations(CNAs)and DNA methylation variation within gene bodies,rather than promoters,are significantly correlated with gene expression variability among these cell cultures.Pathway analysis of CNA/DNA methylation-related genes indicates that a single cell clone from the recurrent tumor exhibits distinct cellular characteristics and tumorigenicity,and such an observation is further confirmed by cellular experiments both in vitro and in vivo.Our systematic analysis reveals that CNAs and epigenomic changes,rather than SNVs,are more likely to contribute to the phenotypic diversity among subpopulations in the tumor.These findings suggest that new therapeutic strategies targeting gene dosage and epigenetic modification should be considered in personalized cancer medicine.This culture model may be applied to the further identification of plausible determinants of cancer metastasis and relapse.
文摘Within the past 10 years, the progress of genomics development in China exhibited a frogleap in terms of scale, quality, organization, and international collaboration. Human genome study has entered a new phase of interdisciplinarity in the history of life science in China. The rise of genomics relied on the development of technology and its integration with other academic disciplines, particularly in the following three areas. First, DNA sequencing technology has been improving its productivity and efficiency at an exponential growth rate. Second, bioinformatics supports the system of data collection, administration, annotation,
基金part of the 10KP (Ten Thousand Plant Genome Sequencing) project https://db.cngb.org/10kp/supported by China National GeneBank (CNGBhttps:// www.cngb.org/)
文摘Micronutrient deficiencies affect more than two billion people worldwide,resulting in poor health,developmental issues,and even death.Iron deficiency is one of the most prevalent micronutrient deficiencies worldwide and impacts approximately one-third of the global population.It can lead to anemia,fatigue.
文摘The colorful,nutrient-rich peels of citrus fruits have long been valued for their tangy flavors and aromatic oils.These oils are produced and stored in special secretory structures called oil glands,which are prevalent across citrus varieties(Knight et al.,2001).Oil glands serve as"reservoirs"for diverse metabolites such as terpenes and flavonoids that give citrus fruits their characteristic aroma(Mahato et al.,2019;Voo et al.,2012;Xian et al.,2022).Many of these compounds also act as chemical defenses against pest and pathogens(Fisher and Phillips,2008).
基金supported by the Projects of International Cooperation and Exchanges from the National Natural Science Foundation of China(Grant No.31161120358)the National Basic Research Program from the Ministry of Science and Technology of China(973 program+3 种基金Grant Nos20111CB510106 and 2015CB910603)the Open Project of State Key Laboratory of Biomembrane and Membrane Biotechnologythe Scientific Research Foundation for Returned Scholars from the Ministry of Education of ChinaML was supported by National Natural Science Foundation of China(Grant No.31400741)
文摘Exosomes are 40–100 nm nano-sized vesicles that are released from many cell types into the extracellular space. Such vesicles are widely distributed in various body fluids. Recently,m RNAs and micro RNAs（mi RNAs） have been identified in exosomes, which can be taken up by neighboring or distant cells and subsequently modulate recipient cells. This suggests an active sorting mechanism of exosomal mi RNAs, since the mi RNA profiles of exosomes may differ from those of the parent cells. Exosomal mi RNAs play an important role in disease progression, and can stimulate angiogenesis and facilitate metastasis in cancers. In this review, we will introduce the origin and the trafficking of exosomes between cells, display current research on the sorting mechanism of exosomal mi RNAs, and briefly describe how exosomes and their mi RNAs function in recipient cells.Finally, we will discuss the potential applications of these mi RNA-containing vesicles in clinical settings.
文摘Dear Editor,Aging is the leading risk factor for many chronic diseases,accounting for almost 60%of all deaths worldwide.How to achieve healthy aging,alleviate aging-related diseases,and extend healthspan has become a main topic of biomedical research(He et al.,2019).Geroprotective compounds,such as metformin and rapamycin,have been shown to improve both healthspan and lifespan in mice(Martin-Montalvo et al.,2013;Bitto et al.,2016),whereas nicotinamide partially improves healthspan in mice(Mitchell et al.,2018).
基金supported by grants from the Mid-Career Researcher Program through the National Research Foundation of Korea funded by the Ministry of Science,ICT and Future Planning(NRF2021R1A2C1004187)Republic of Korea,the Jiangsu Agricultural Science and Technology Innovation Fund(JASTIF+1 种基金grant CX(22)3168)the Qing Lan Project of Jiangsu Province(2024).
文摘N^(6)-methyladenosine(m^(6)A)is the most abundant modification observed in eukaryotic mRNAs.Advances in transcriptome-wide m^(6)A mapping and sequencing technologies have enabled the identification of several conserved motifs in plants,including the RRACH(R=A/G and H=A/C/U)and UGUAW(W=U or A)motifs.However,the mechanisms underlying deposition of m^(6)A marks at specific positions in the conserved motifs of individual transcripts remain to be clarified.Evidence from plant and animal studies suggests that m^(6)A writer or eraser components are recruited to specific genomic loci through interactions with particular transcription factors,5-methylcytosine DNA methylation marks,and histone marks.In addition,recent studies in animal cells have shown that microRNAs play a role in depositing m^(6)A marks at specific sites in transcripts through a base-pairing mechanism.m^(6)A also affects the biogenesis and function of chromatin-associated regulatory RNAs and long noncoding RNAs.Although we have less of an understanding of the link between m^(6)A modification and epigenetic factors in plants than in animals,recent progress in identifying the proteins that interact with m^(6)A writer or eraser components has provided insights into the crosstalk between m^(6)A modification and epigenetic factors,which plays a crucial role in transcript-specific methylation and regulation of m^(6)A in plants.
基金supported by the National Natural Science Foundation of China (91754204)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16010107)+5 种基金National Key Research and Development Program of China (2018YFA0108500, 2017YFC1001001)the National NaturalScience Foundation of China (81630078, 31670822, 31401151, 31570816, 81371415)the Natural Science Foundation of Beijing (5181001)CAS Strategic Priority Research Program (XDB14030300)the State Key Laboratory of Membrane Biologythe Key Laboratory of Genomic and Precision Medicine
文摘PINK1/Parkin-mediated mitophagy is an important process in selective removal of damaged mitochondria, in which translocation of Parkin to damaged mitochondria is recognized as an initiation step. At present, how the damaged mitochondria are selectively recognized and targeted by Parkin is not fully understood. Here we show that Miro2, an outer mitochondrial membrane protein, undergoes demultimerization from a tetramer to a monomer and alteration in mitochondrial localization upon CCCP treatment, suggesting a CCCP-induced realignment of Miro2. The realignment of Miro2 is tightly regulated by PINK1-mediated phosphorylation at Ser325/Ser430 and by Ca^2+binding to EF2 domain, which are both essential for the subsequent Parkin translocation. Interestingly, ablation of Miro2 in mouse causes delayed reticulocyte maturation, lactic acidosis and cardiac disorders. Furthermore, several Miro2 mutations found in the congenital lactic acidosis patients also disable its realignment and Parkin translocation. These findings reveal an important role of Miro2 to mediate Parkin translocation by sensing both depolarization and Ca^2+release from damaged mitochondria to ensure the accuracy of mitophagy.
基金supported by the Science,Technology and Innovation Commission of Shenzhen Municipality under grant No.JCYJ20170303151334808 and grant No.JSGG20180508152912700The first author would like to acknowledge financial support from the China Scholarship Council(CSC)(grant No.201904910476).
文摘T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus(CMV)infection1 and the ongoing COVID-19 pandemic caused by SARS-CoV-2.^(2) CMV-related diseases occur once the host immune system is impaired or lacks a protective repertoire of virus-specific T lymphocytes.3 Adoptive transfer of T-cell receptor(TCR)-engineered T cells(TCR-Ts)provides an encouraging alternative treatment option for patients with CMV reactivation.^(4) However,generating TCR-Ts requires the identification of epitope-specific and functional TCR pairs.Modern single-cell sequencing techniques open up the ability to unravel TCR repertoires,^(5 )which offers a potential opportunity to screen functional TCR pairs for TCR-T therapy.Here,we report an efficient approach that combines ex vivo CD8+T-cell stimulation with single-cell RNA and TCR V(D)J sequencing to identify CMV-specific TCRs for generating TCR-Ts.
