Modern land plants comprise two main lineages:tracheophytes and bryophytes.The latter include mosses,liverworts,and hornworts.Bryophytes are second only to angiosperms in diversity,with approximately 22,000 species(Sh...Modern land plants comprise two main lineages:tracheophytes and bryophytes.The latter include mosses,liverworts,and hornworts.Bryophytes are second only to angiosperms in diversity,with approximately 22,000 species(Shaw,2008).They are characterized by a life cycle dominated by haploid gametophytes,with unbranched diploid sporophytes attached to the gametophytes,producing spores for sexual reproduction(Shaw and Renzaglia,2004).Bryophytes have demonstrated great adaptability to modern ecosystems,thriving in environments ranging from deserts to wetlands and from tropical to polar regions(Degola et al.,2022).This adaptability suggests that bryophytes may have evolved an effective genetic toolkit for stress tolerance.Advances in genome sequencing and assembly technologies offer great opportunities to decipher the genetic toolkit and study the evolution of resistance and environmental adaptation in bryophytes.展开更多
Marchantia polymorpha,a model liverwort,provides a valuable system for investigating the evolution of plant sexual reproduction.To explore the cellular landscape of its reproductive structures,we generate a single-nuc...Marchantia polymorpha,a model liverwort,provides a valuable system for investigating the evolution of plant sexual reproduction.To explore the cellular landscape of its reproductive structures,we generate a single-nucleus transcriptomic atlas of the antheridiophore,archegoniophore,and sporophyte.Using singlenucleus RNA sequencing(snRNA-seq),we capture over 30,000 high-quality nuclei and identify distinct cel populations.In the male organ,we characterize stages of spermatogenesis from early antheridium cells to mature sperm,revealing dynamic transcriptional programs including cell cycle regulation,chromatin remodeling,and calcium signaling.In the female organ,we define cell types including archegonial layers and secondary central cells.Sporophyte clusters are annotated as spores,elaters,capsule wall,foot,and seta cells,with transcriptional signatures related to structural support,stress response,and reproductive functions.Cross-species analysis indicates that capsule wall cells in liverworts are similar to tapetum cells.Notably,foot cells exhibit high expression of genes involved in sporopollenin biosynthesis and signaling pathways,serving as a central hub that mediates communication between the maternal gametophyte and the developing sporophyte.This study provides a comprehensive cellular and molecular map of M.polymorpha reproductive organs and sporophyte,establishing a framework for investigating the development and evolution of sexual reproduction in early land plants.展开更多
Handedness is a fundamental behavioral trait in humans,with the majority exhibiting right-hand dominance.While its origins remain elusive,it is considered an innate genetic trait.This study demonstrates pawedness in m...Handedness is a fundamental behavioral trait in humans,with the majority exhibiting right-hand dominance.While its origins remain elusive,it is considered an innate genetic trait.This study demonstrates pawedness in mice(n=473),comparable to human handedness,as an acquired trait rapidly emerging after limited unilateral paw training.Notably,acquired right-pawedness demonstrates greater conservativeness compared to left-pawedness,as evidenced by stronger stability and greater resistance to reversal.This results in a population right-paw dominance under random training conditions.Moreover,acquired pawedness also exhibits sex differences,with the initial preference proving more malleable in females.These findings unveil the acquired features of pawedness in mice.By illuminating possible behavioral laterality commonalities across species,the study proposes a postnatal hypothesis for the origins of human handedness:it is not an innate genetic trait as traditionally believed,but rather an environmentally acquired stable behavior whose development is actively guided by genetic predispositions.展开更多
目的 评估孕期居住地周边绿地暴露与低出生体重(low birth weight,LBW,出生体重<2 500 g)风险的关联。方法 本研究为回顾性队列研究,基于既有多中心母婴队列数据库(重庆、贵阳、成都、连云港)开展二次分析。回顾性纳入2023年12月—2...目的 评估孕期居住地周边绿地暴露与低出生体重(low birth weight,LBW,出生体重<2 500 g)风险的关联。方法 本研究为回顾性队列研究,基于既有多中心母婴队列数据库(重庆、贵阳、成都、连云港)开展二次分析。回顾性纳入2023年12月—2024年12月在四中心分娩并符合纳排标准的单胎妊娠孕妇,提取其孕期及分娩相关资料,并采用MODIS MOD13Q1估计居住地500 m缓冲区归一化植被指数均值(normalized difference vegetation index mean within 500 m buffer,NDVImean-500 m)与增强型植被指数均值(enhanced vegetation index mean within 500 m buffer,EVImean-500 m)。以LBW为二分类结局,采用Logistic回归评估NDVI/EVI(每增加0.1单位)与LBW风险的关联,并构建限制性立方样条(restricted cubic spline,RCS)评估剂量―反应关系。多因素模型(Model 2)调整高龄(≥35岁)、受教育程度、孕前体重指数(body mass index,BMI)分组与产次。另在Model 2基础上开展“附加调整孕周(<37周)”及“足月限制(≥37周)”敏感性分析。结果 共纳入单胎孕妇5 397例,其中LBW 147例,发生率为2.72%(95%CI:2.32%~3.19%)。在完全调整模型中,EVImean-500 m每增加0.1单位与LBW风险降低相关(OR=0.488,95%CI:0.405~0.587,P<0.001),NDVImean-500 m结果一致(OR=0.690,95%CI:0.587~0.810,P<0.001)。RCS分析显示,2个指标总体关联均显著(P<0.001);EVI提示非线性(P<0.001),NDVI未见显著非线性(P=0.095)。附加调整孕周及足月限制后,关联方向与主分析一致。结论 在单胎妊娠样本中,孕期居住地周边绿地暴露水平与LBW风险降低相关,并呈现剂量―反应特征。鉴于观察性研究可能存在残余混杂与暴露错分,结果应谨慎解释为相关性发现,尚需进一步研究验证其因果关系与作用路径。展开更多
The amniote pallium,a vital component of the forebrain,exhibits considerable evolutionary divergence across species and mediates diverse functions,including sensory processing,memory formation,and learning.However,the...The amniote pallium,a vital component of the forebrain,exhibits considerable evolutionary divergence across species and mediates diverse functions,including sensory processing,memory formation,and learning.However,the relationships among pallial subregions in different species remain poorly characterized,particularly regarding the identification of homologous neurons and their transcriptional signatures.In this study,we utilized singlenucleus RNA sequencing to examine over 130?000 nuclei from the macaque(Macaca fascicularis)neocortex,complemented by datasets from humans(Homo sapiens),mice(Mus musculus),zebra finches(Taeniopygia guttata),turtles(Chrysemys picta bellii),and lizards(Pogona vitticeps),enablingcomprehensivecross-species comparison.Results revealed transcriptomic conservation and species-specific distinctions within the amniote pallium.Notable similarities were observed among cell subtypes,particularly within PVALB+inhibitory neurons,which exhibited species-preferred subtypes.Furthermore,correlations between pallial subregions and several transcription factor candidates were identified,including RARB,DLX2,STAT6,NR3C1,and THRB,with potential regulatory roles in gene expression in mammalian pallial neurons compared to their avian and reptilian counterparts.These results highlight the conserved nature of inhibitory neurons,remarkable regional divergence of excitatory neurons,and species-specific gene expression and regulation in amniote pallial neurons.Collectively,these findings provide valuable insights into the evolutionary dynamics of the amniote pallium.展开更多
CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identif...CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identifying protospacer adjacent motif(PAM)sequences.Due to the limitations of experimental methods,bioinformatics approaches have become essential.However,existing PAM prediction programs are limited by the small number of spacers in CRISPR-Cas systems,resulting in low accuracy.To address this,we develop PAMPHLET,a pipeline that uses homology searches to identify additional spacers,significantly increasing the number of spacers up to 18-fold.PAMPHLET is validated on 20 CRISPR-Cas systems and successfully predicts PAM sequences for 18 protospacers.These predictions are further validated using the DocMF platform,which characterizes protein-DNA recognition patterns via next-generation sequencing.The high consistency between PAMPHLET predictions and DocMF results for Cas proteins demonstrates the potential of PAMPHLET to enhance PAM sequence prediction accuracy,expedite the discovery process,and accelerate the development of CRISPR tools.展开更多
Inbreeding increases genome homozygosity within populations,which can exacerbate inbreeding depression by exposing homozygous deleterious alleles that are responsible for declines in fitness traits.In small population...Inbreeding increases genome homozygosity within populations,which can exacerbate inbreeding depression by exposing homozygous deleterious alleles that are responsible for declines in fitness traits.In small populations,genetic purging that occurs under the pressure of natural selection acts as an opposing force,contributing to a reduction of deleterious alleles.Both inbreeding and genetic purging are paramount in the field of conservation genomics.The Amur tiger(Panthera tigris altaica)lives in small populations in the forests of Northeast Asia and is among the most endangered animals on the planet.Using genome-wide assessment and comparison,we reveal substantially higher and more extensive inbreeding in wild Amur tigers(F_(ROH)=0.50)than in captive individuals(F_(ROH)=0.24).However,a relatively reduced number of lossof-function mutations in wild Amur tigers is observed compared to captive individuals,indicating genetic purging of inbreeding load with relatively large-effect alleles.The higher ratio of homozygous mutation load and number of fixed damaging alleles in the wild population indicates a less-efficient genetic purging,with purifying selection also contributing to this process.These findings provide valuable insights for the future conservation of Amur tigers.展开更多
Germ-free mice exhibit profound immunological immaturity.Despite recent studies emphasizing the role of specific bacterium-derived metabolites in immune cell development and differentiation,the mechanisms linking micr...Germ-free mice exhibit profound immunological immaturity.Despite recent studies emphasizing the role of specific bacterium-derived metabolites in immune cell development and differentiation,the mechanisms linking microbiota absence to systemic immune deficits remain incompletely defined.Here,droplet-based single-cell RNA sequencing of bone marrow and peripheral blood from both germ-free and specific pathogen-free mice was performed,identifying 25 transcriptionally distinct cell types.Neutrophil apoptosis was elevated in germ-free mice,potentially due to the absence of niacin dehydrogenase,a metabolite primarily produced by Pseudomonas.In addition,germ-free mice exhibited increased excretion of 5’-methylthioadenosine,enhanced ERK activation driven by reactive oxygen species,and disruption of bone marrow stromal antigen 2 signaling.Monocytes and CD8^(+)T cells from germ-free mice showed diminished responses to interferon-β and interferon-γ,consistent with heightened viral susceptibility.These findings establish a microbiota-dependent regulatory pathway linking immunodeficiency to microbial absence in germ-free mice,confirmed through complementary validation techniques.展开更多
Colorectal cancer(CRC)is a major contributor to global cancer-related mortality with increasing incidence rates in both developed and developing regions.Therefore,CRC presents a significant challenge to global health....Colorectal cancer(CRC)is a major contributor to global cancer-related mortality with increasing incidence rates in both developed and developing regions.Therefore,CRC presents a significant challenge to global health.The development of innovative tools for enhancing early CRC screening and diagnosis,along with novel treatments and therapies for improved management,remains an urgent necessity.CRC is intricately associated with the gut microbiota,which is integral to food digestion,nutrient generation,drug metabolism,metabolite production,immune enhancement,endocrine regulation,neurogenesis modulation,and the maintenance of physiologic and psychological equilibrium.Dysbiosis or imbalances in the gut microbiome have been implicated in various disorders,including CRC.Emerging evidence highlights the critical role of the gut microbiome in CRC pathogenesis and treatment,which presents potential opportunities for early detection and diagnosis.Despite substantial advances in understanding the relationship between the gut microbiota and CRC,significant challenges persist.Gaining a deeper and more detailed understanding of the interactions between the human microbiota and cancer is essential to fully realize the potential of the microbiota in cancer management.Unlike genetic factors,the gut microbiome is subject to modification,offering a promising avenue for the development of CRC treatments and drug discovery.This review provides an overview of the interactions between the human gut microbiome and CRC,while examining prospects for precision management of CRC.展开更多
基金funded by Scientific Foundation of the Urban Management Bureau of Shenzhen(202403 to YL and 202302 to SD)part of the 10KP project(https://db.cngb.org/10kp/)+1 种基金supported by China National GeneBank(CNGBhttps://www.cngb.org/).
文摘Modern land plants comprise two main lineages:tracheophytes and bryophytes.The latter include mosses,liverworts,and hornworts.Bryophytes are second only to angiosperms in diversity,with approximately 22,000 species(Shaw,2008).They are characterized by a life cycle dominated by haploid gametophytes,with unbranched diploid sporophytes attached to the gametophytes,producing spores for sexual reproduction(Shaw and Renzaglia,2004).Bryophytes have demonstrated great adaptability to modern ecosystems,thriving in environments ranging from deserts to wetlands and from tropical to polar regions(Degola et al.,2022).This adaptability suggests that bryophytes may have evolved an effective genetic toolkit for stress tolerance.Advances in genome sequencing and assembly technologies offer great opportunities to decipher the genetic toolkit and study the evolution of resistance and environmental adaptation in bryophytes.
基金supported by the 10 KP project(https://db.cngb.org/1Okp/)and the Scientific Foundation of the Urban Management Bureau of Shenzhen(202403).
文摘Marchantia polymorpha,a model liverwort,provides a valuable system for investigating the evolution of plant sexual reproduction.To explore the cellular landscape of its reproductive structures,we generate a single-nucleus transcriptomic atlas of the antheridiophore,archegoniophore,and sporophyte.Using singlenucleus RNA sequencing(snRNA-seq),we capture over 30,000 high-quality nuclei and identify distinct cel populations.In the male organ,we characterize stages of spermatogenesis from early antheridium cells to mature sperm,revealing dynamic transcriptional programs including cell cycle regulation,chromatin remodeling,and calcium signaling.In the female organ,we define cell types including archegonial layers and secondary central cells.Sporophyte clusters are annotated as spores,elaters,capsule wall,foot,and seta cells,with transcriptional signatures related to structural support,stress response,and reproductive functions.Cross-species analysis indicates that capsule wall cells in liverworts are similar to tapetum cells.Notably,foot cells exhibit high expression of genes involved in sporopollenin biosynthesis and signaling pathways,serving as a central hub that mediates communication between the maternal gametophyte and the developing sporophyte.This study provides a comprehensive cellular and molecular map of M.polymorpha reproductive organs and sporophyte,establishing a framework for investigating the development and evolution of sexual reproduction in early land plants.
基金supported by grants from the National Natural Science Foundation of China,China(32470630 to Z.S.)the Scientific Foundation of the Institute of Psychology,Chinese Academy of Sciences,China(E2CX4115CX to J.W.)State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management,China(SKLA2508 to Y.W.).
文摘Handedness is a fundamental behavioral trait in humans,with the majority exhibiting right-hand dominance.While its origins remain elusive,it is considered an innate genetic trait.This study demonstrates pawedness in mice(n=473),comparable to human handedness,as an acquired trait rapidly emerging after limited unilateral paw training.Notably,acquired right-pawedness demonstrates greater conservativeness compared to left-pawedness,as evidenced by stronger stability and greater resistance to reversal.This results in a population right-paw dominance under random training conditions.Moreover,acquired pawedness also exhibits sex differences,with the initial preference proving more malleable in females.These findings unveil the acquired features of pawedness in mice.By illuminating possible behavioral laterality commonalities across species,the study proposes a postnatal hypothesis for the origins of human handedness:it is not an innate genetic trait as traditionally believed,but rather an environmentally acquired stable behavior whose development is actively guided by genetic predispositions.
文摘目的 评估孕期居住地周边绿地暴露与低出生体重(low birth weight,LBW,出生体重<2 500 g)风险的关联。方法 本研究为回顾性队列研究,基于既有多中心母婴队列数据库(重庆、贵阳、成都、连云港)开展二次分析。回顾性纳入2023年12月—2024年12月在四中心分娩并符合纳排标准的单胎妊娠孕妇,提取其孕期及分娩相关资料,并采用MODIS MOD13Q1估计居住地500 m缓冲区归一化植被指数均值(normalized difference vegetation index mean within 500 m buffer,NDVImean-500 m)与增强型植被指数均值(enhanced vegetation index mean within 500 m buffer,EVImean-500 m)。以LBW为二分类结局,采用Logistic回归评估NDVI/EVI(每增加0.1单位)与LBW风险的关联,并构建限制性立方样条(restricted cubic spline,RCS)评估剂量―反应关系。多因素模型(Model 2)调整高龄(≥35岁)、受教育程度、孕前体重指数(body mass index,BMI)分组与产次。另在Model 2基础上开展“附加调整孕周(<37周)”及“足月限制(≥37周)”敏感性分析。结果 共纳入单胎孕妇5 397例,其中LBW 147例,发生率为2.72%(95%CI:2.32%~3.19%)。在完全调整模型中,EVImean-500 m每增加0.1单位与LBW风险降低相关(OR=0.488,95%CI:0.405~0.587,P<0.001),NDVImean-500 m结果一致(OR=0.690,95%CI:0.587~0.810,P<0.001)。RCS分析显示,2个指标总体关联均显著(P<0.001);EVI提示非线性(P<0.001),NDVI未见显著非线性(P=0.095)。附加调整孕周及足月限制后,关联方向与主分析一致。结论 在单胎妊娠样本中,孕期居住地周边绿地暴露水平与LBW风险降低相关,并呈现剂量―反应特征。鉴于观察性研究可能存在残余混杂与暴露错分,结果应谨慎解释为相关性发现,尚需进一步研究验证其因果关系与作用路径。
基金supported by the National Key Research and Development Program (2022YEF0203200)National Science and Technology Innovation 2030 Major Program (STI2030-2021ZD0200100)National Key Research and Development Program (2018YFA0801400,2021YFA0805100)。
文摘The amniote pallium,a vital component of the forebrain,exhibits considerable evolutionary divergence across species and mediates diverse functions,including sensory processing,memory formation,and learning.However,the relationships among pallial subregions in different species remain poorly characterized,particularly regarding the identification of homologous neurons and their transcriptional signatures.In this study,we utilized singlenucleus RNA sequencing to examine over 130?000 nuclei from the macaque(Macaca fascicularis)neocortex,complemented by datasets from humans(Homo sapiens),mice(Mus musculus),zebra finches(Taeniopygia guttata),turtles(Chrysemys picta bellii),and lizards(Pogona vitticeps),enablingcomprehensivecross-species comparison.Results revealed transcriptomic conservation and species-specific distinctions within the amniote pallium.Notable similarities were observed among cell subtypes,particularly within PVALB+inhibitory neurons,which exhibited species-preferred subtypes.Furthermore,correlations between pallial subregions and several transcription factor candidates were identified,including RARB,DLX2,STAT6,NR3C1,and THRB,with potential regulatory roles in gene expression in mammalian pallial neurons compared to their avian and reptilian counterparts.These results highlight the conserved nature of inhibitory neurons,remarkable regional divergence of excitatory neurons,and species-specific gene expression and regulation in amniote pallial neurons.Collectively,these findings provide valuable insights into the evolutionary dynamics of the amniote pallium.
基金supported by grants from the Foundation for Distinguished Young Talents in Higher Education of Guangdong,China(2024KQNCX157)Our work was also supported in part by the Guangdong Provincial Key Laboratory of Interdisciplinary Research and Application for Data Science,BNU-HKBU United International College(2022B1212010006)+1 种基金in part by the Guangdong Higher Education Upgrading Plan(2021-2025)of“Rushing to the Top,Making Up Shortcomings and Strengthening Special Features”(R0400001-22)Additionally,we acknowledge support from the Zhuhai Basic and Applied Basic ResearchFoundation(2220004002717).
文摘CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identifying protospacer adjacent motif(PAM)sequences.Due to the limitations of experimental methods,bioinformatics approaches have become essential.However,existing PAM prediction programs are limited by the small number of spacers in CRISPR-Cas systems,resulting in low accuracy.To address this,we develop PAMPHLET,a pipeline that uses homology searches to identify additional spacers,significantly increasing the number of spacers up to 18-fold.PAMPHLET is validated on 20 CRISPR-Cas systems and successfully predicts PAM sequences for 18 protospacers.These predictions are further validated using the DocMF platform,which characterizes protein-DNA recognition patterns via next-generation sequencing.The high consistency between PAMPHLET predictions and DocMF results for Cas proteins demonstrates the potential of PAMPHLET to enhance PAM sequence prediction accuracy,expedite the discovery process,and accelerate the development of CRISPR tools.
基金supported by the Fundamental Research Funds for the Central Universities of China(2572022DQ03)the National Natural Science Foundation of China(32170517)+2 种基金the Guangdong Provincial Key Laboratory of Genome Read and Write(2017B030301011)the Start-up Scientific Foundation of Northeast Forestry University(60201524043)supported by China National GeneBank(CNGB).
文摘Inbreeding increases genome homozygosity within populations,which can exacerbate inbreeding depression by exposing homozygous deleterious alleles that are responsible for declines in fitness traits.In small populations,genetic purging that occurs under the pressure of natural selection acts as an opposing force,contributing to a reduction of deleterious alleles.Both inbreeding and genetic purging are paramount in the field of conservation genomics.The Amur tiger(Panthera tigris altaica)lives in small populations in the forests of Northeast Asia and is among the most endangered animals on the planet.Using genome-wide assessment and comparison,we reveal substantially higher and more extensive inbreeding in wild Amur tigers(F_(ROH)=0.50)than in captive individuals(F_(ROH)=0.24).However,a relatively reduced number of lossof-function mutations in wild Amur tigers is observed compared to captive individuals,indicating genetic purging of inbreeding load with relatively large-effect alleles.The higher ratio of homozygous mutation load and number of fixed damaging alleles in the wild population indicates a less-efficient genetic purging,with purifying selection also contributing to this process.These findings provide valuable insights for the future conservation of Amur tigers.
基金supported by the Science Technology and Innovation Commission of Shenzhen Municipality,China(SGCX20190919142801722)。
文摘Germ-free mice exhibit profound immunological immaturity.Despite recent studies emphasizing the role of specific bacterium-derived metabolites in immune cell development and differentiation,the mechanisms linking microbiota absence to systemic immune deficits remain incompletely defined.Here,droplet-based single-cell RNA sequencing of bone marrow and peripheral blood from both germ-free and specific pathogen-free mice was performed,identifying 25 transcriptionally distinct cell types.Neutrophil apoptosis was elevated in germ-free mice,potentially due to the absence of niacin dehydrogenase,a metabolite primarily produced by Pseudomonas.In addition,germ-free mice exhibited increased excretion of 5’-methylthioadenosine,enhanced ERK activation driven by reactive oxygen species,and disruption of bone marrow stromal antigen 2 signaling.Monocytes and CD8^(+)T cells from germ-free mice showed diminished responses to interferon-β and interferon-γ,consistent with heightened viral susceptibility.These findings establish a microbiota-dependent regulatory pathway linking immunodeficiency to microbial absence in germ-free mice,confirmed through complementary validation techniques.
基金the Hangzhou Institute of Medicine(HIM)and Chinese Academy of Sciences for supporting work of this article。
文摘Colorectal cancer(CRC)is a major contributor to global cancer-related mortality with increasing incidence rates in both developed and developing regions.Therefore,CRC presents a significant challenge to global health.The development of innovative tools for enhancing early CRC screening and diagnosis,along with novel treatments and therapies for improved management,remains an urgent necessity.CRC is intricately associated with the gut microbiota,which is integral to food digestion,nutrient generation,drug metabolism,metabolite production,immune enhancement,endocrine regulation,neurogenesis modulation,and the maintenance of physiologic and psychological equilibrium.Dysbiosis or imbalances in the gut microbiome have been implicated in various disorders,including CRC.Emerging evidence highlights the critical role of the gut microbiome in CRC pathogenesis and treatment,which presents potential opportunities for early detection and diagnosis.Despite substantial advances in understanding the relationship between the gut microbiota and CRC,significant challenges persist.Gaining a deeper and more detailed understanding of the interactions between the human microbiota and cancer is essential to fully realize the potential of the microbiota in cancer management.Unlike genetic factors,the gut microbiome is subject to modification,offering a promising avenue for the development of CRC treatments and drug discovery.This review provides an overview of the interactions between the human gut microbiome and CRC,while examining prospects for precision management of CRC.
