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中国科学:生命科学（英文版）
中国科学:生命科学（英文版）

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中国科学:生命科学（英文版）/Journal Science China(Life Sciences)CSCDCSTPCDSCI
查看更多>>《中国科学》是中国科学院主办、中国科学杂志社出版的自然科学专业性学术刊物。《中国科学》任务是反映中国自然科学各学科中的最新科研成果，以促进国内外的学术交流。《中国科学》以论文形式报道中国基础研究和应用研究方面具有创造性的、高水平的和有重要意义的科研成果。在国际学术界，《中国科学》作为代表中国最高水平的学术刊物也受到高度重视。国际上最具有权威的检索刊物SCI，多年来一直收录《中国科学》的论文。1999年《中国科学》夺得国家期刊奖的第一名。
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    A CRISPR/RfxCas13d-mediated strategy for efficient RNA knockdown in mouse embryonic development

    Lin ZhangShi-Meng CaoHao WuMeng Yan...
    2297-2306页
    查看更多>>摘要：The growing variety of RNA classes,such as mRNAs,IncRNAs,and circRNAs,plays pivotal roles in both developmental processes and various pathophysiological conditions.Nonetheless,our comprehension of RNA functions in live organisms remains limited due to the absence of durable and effective strategies for directly influencing RNA levels.In this study,we combined the CRISPR-RfxCas13d system with sperm-like stem cell-mediated semi-cloning techniques,which enabled the suppressed expression of different RNA species.This approach was employed to interfere with the expression of three types of RNA molecules:Sfmbt2 mRNA,Fendrr IncRNA,and circMan1a2(2,3,4,5,6).The results confirmed the critical roles of these RNAs in embryonic development,as their loss led to observable phenotypes,including embryonic lethality,delayed embryonic development,and embryo resorption.In summary,our methodology offers a potent toolkit for silencing specific RNA targets in living organisms without introducing genetic alterations.
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    Single-cell immune landscape of measurable residual disease in acute myeloid leukemia

    Xiaodong MoWeilong ZhangGuomei FuYingjun Chang...
    2307-2322页
    查看更多>>摘要：Measurable residual disease(MRD)is a powerful prognostic factor of relapse in acute myeloid leukemia(AML).We applied the single-cell RNA sequencing to bone marrow(BM)samples from patients with(n=20)and without(n=12)MRD after allogeneic hematopoietic stem cell transplantation.A comprehensive immune landscape with 184,231 cells was created.Compared with CD8+T cells enriched in the MRD-negative group(MRD-_CD8),those enriched in the MRD-positive group(MRD+_CD8)showed lower expression levels of cytotoxicity-related genes.Three monocyte clusters(i.e.,MRD+_M)and three B-cell clusters(i.e.,MRD+_B)were enriched in the MRD-positive group.Con-version from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD-_CD8 clusters and vice versa.MRD-enriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD-_CD8 clusters.These findings revealed the characteristics of the immune cell landscape in MRD positivity,which will allow for a better understanding of the immune mechanisms for MRD conversion.
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    COVID-19 vaccine updates for people under different conditions

    Yijiao HuangWeiyang WangYan LiuZai Wang...
    2323-2343页
    查看更多>>摘要：SARS-CoV-2 has caused global waves of infection since December 2019 and continues to persist today.The emergence of SARS-CoV-2 variants with strong immune evasion capabilities has compromised the effectiveness of existing vaccines against breakthrough infections.Therefore,it is important to determine the best utilization strategies for different demographic groups given the variety of vaccine options available.In this review,we will discuss the protective efficacy of vaccines during different stages of the epidemic and emphasize the importance of timely updates to target prevalent variants,which can significantly improve immune protection.While it is recognized that vaccine effectiveness may be lower in certain populations such as the elderly,individuals with chronic comorbidities(e.g.,diabetes with poor blood glucose control,those on maintenance dialysis),or those who are immunocompromised compared to the general population,administering multiple doses can result in a strong protective immune response that outweighs potential risks.However,caution should be exercised when considering vaccines that might trigger an intense immune response in populations prone to inflammatory flare or other complications.In conclusion,individuals with special conditions require enhanced and more effective immunization strategies to prevent infection or reinfection,as well as to avoid the potential development of long COVID.
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    Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutation

    Qian HaoJinfeng LiLeng-Siew Yeap
    2344-2353页
    查看更多>>摘要：Antibody diversification is essential for an effective immune response,with somatic hypermutation(SHM)serving as a key molecular process in this adaptation.Activation-induced cytidine deaminase(AID)initiates SHM by inducing DNA lesions,which are ultimately resolved into point mutations,as well as small insertions and deletions(indels).These mutational outcomes contribute to antibody affinity maturation.The mechanisms responsible for generating point mutations and indels involve the base excision repair(BER)and mismatch repair(MMR)pathways,which are well coordinated to maintain genomic integrity while allowing for beneficial mutations to occur.In this regard,translesion synthesis(TLS)polymerases contribute to the diversity of mutational outcomes in antibody genes by enabling the bypass of DNA lesions.This review summarizes our current understanding of the distinct molecular mechanisms that generate point mutations and indels during SHM.Understanding these mechanisms is critical for elucidating the development of broadly neutralizing antibodies(bnAbs)and autoantibodies,and has implications for vaccine design and therapeutics.
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    Role of macrophages in aortic dissection pathogenesis:insights from preclinical studies to translational prospective

    Shiyi LiWeiguo FuLixin Wang
    2354-2367页
    查看更多>>摘要：Aortic dissection is a critical vascular disease that is characterized by a high mortality rate and inflammation significantly influences its onset and progression.Recent studies highlight the integral role of macrophages,key players in the immune system,in the pathological landscape of aortic dissection.These cells are involved in crucial processes,such as the remodeling of the extracellular matrix,immunocyte infiltration,and phenotypic switching of smooth muscle cells,which are essential for the structural integrity and functional dynamics of the aortic wall.Despite these insights,the specific contributions of macrophages to the development and progression of aortic dissection remains unclear.This review explores the pathogenesis of aortic dissection with a focus on macrophages and describes their origins,phenotypic variations,and potential roles based on the most recent research findings.Furthermore,we discuss key molecules related to macrophages during aortic dissection,their interactions with other cellular components within the aorta,and the implications of these interactions for future therapeutic strategies.This comprehensive analysis aimed to improve our understanding of macrophages in aortic dissection and promote the development of targeted interventions.
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    Whole-genome sequencing identifies novel genes for autism in Chinese trios

    Suhua ChangJia Jia LiuYilu ZhaoTao Pang...
    2368-2381页
    查看更多>>摘要：Autism spectrum disorder(ASD)is a neurodevelopmental disorder with high genetic heritability but heterogeneity.Fully understanding its genetics requires whole-genome sequencing(WGS),but the ASD studies utilizing WGS data in Chinese population are limited.In this study,we present a WGS study for 334 individuals,including 112 ASD patients and their non-ASD parents.We identified 146 de novo variants in coding regions in 85 cases and 60 inherited variants in coding regions.By integrating these variants with an association model,we identified 33 potential risk genes(P＜0.001)enriched in neuron and regulation related biological process.Besides the well-known ASD genes(SCN2A,NF1,SHANK3,CHD8 etc.),several high confidence genes were highlighted by a series of functional analyses,including CTNND1,DGKZ,LRP1,DDN,ZNF483,NR4A2,SMAD6,INTS1,and MRPL12,with more supported evidence from GO enrichment,expression and network analysis.We also integrated RNA-seq data to analyze the effect of the variants on the gene expression and found 12 genes in the individuals with the related variants had relatively biased expression.We further presented the clinical phenotypes of the proband carrying the risk genes in both our samples and Caucasian samples to show the effect of the risk genes on phenotype.Regarding variants in non-coding regions,a total of 74 de novo variants and 30 inherited variants were predicted as pathogenic with high confidence,which were mapped to specific genes or regulatory features.The number of de novo variants found in patient was significantly associated with the parents'ages at the birth of the child,and gender with trend.We also identified small de novo structural variants in ASD trios.The results in this study provided important evidence for understanding the genetic mechanism of ASD.
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    Activation of the PGC-1 α-media ted mitochondrial glutamine metabolism pathway attenuates female offspring osteoarthritis induced by prenatal excessive prednisone

    Qingxian LiFan ZhangYongguo DaiLiang Liu...
    2382-2397页
    查看更多>>摘要：Osteoarthritis is a chronic,age-related joint disease.Previous studies have shown that osteoarthritis develops during intrauterine devel-opment.Prednisone is frequently used to treat pregnancies complicated by autoimmune diseases.However,limited research has been conducted on the enduring effects of prednisone use during pregnancy on the offspring.In this study,we investigated the effect of excessive prednisone exposure on cartilage development and susceptibility to osteoarthritis in the offspring.We found that prenatal prednisone exposure(PPE)impaired cartilage extracellular matrix(ECM)synthesis,resulting in poor cartilage pathology in female offspring during the adult period,which was further exacerbated after long-distance running stimulation.Additionally,PPE suppressed cartilage development during the intrauterine period.Tracing back to the intrauterine period,we found that Pred,rather than prednisone,decreased glutamine metabolic flux,which resulted in increased oxidative stress,and decreased histone acetylation,and expression of cartilage phenotypic genes.Further,PGC-1α-mediated mitochondrial biogenesis,while PPE caused hypermethylation in the promoter region of PGC-1α and decreased its expression in fetal cartilage by activating the glucocorticoid receptor,resulting in a reduction of glutamine flux controlled by mitochondrial biogenesis.Additionally,overexpression of PGC-1α(either pharmacological or through lentiviral transfection)reversed PPE-and Pred-induced cartilage ECM synthesis impairment.In summary,this study demonstrated that PPE causes chondrodysplasia in female offspring and increases their susceptibility to postnatal osteoarthritis.Hence,targeting PGC-1α early on could be a potential intervention strategy for PPE-induced osteoarthritis susceptibility.
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    The single-cell transcriptomic landscape of the topological differences in mammalian auditory receptors

    Xiangyu MaXin ChenYuwei CheSiyao Zhu...
    2398-2410页
    查看更多>>摘要：Mammalian hair cells(HCs)are arranged spirally along the cochlear axis and correspond to different frequency ranges.Serving as primary sound detectors,HCs spatially segregate component frequencies into a topographical map.HCs display significant diversity in anatomical and physiological characteristics,yet little is known about the organization of the cochleotopic map of HCs or the molecules involved in this process.Using single-cell RNA sequencing,we determined the distinct molecular profiles of inner hair cells and outer hair cells,and we identified numerous position-dependent genes that were expressed as gradients.Newly identified genes such as Ptn,Rxra,and Nfe212 were found to be associated with tonotopy.We employed the SCENIC algorithm to predict the transcription factors that potentially shape these tonotopic gradients.Furthermore,we confirmed that Nfe212,a tonotopy-related transcription factor,is critical in mice for sensing low-to-medium sound frequencies in vivo.the analysis of cell-cell communication revealed potential receptor-ligand networks linking inner hair cells to spiral ganglion neurons,including pathways such as BDNF-Ntrk and PTN-Scd4,which likely play essential roles in tonotopic maintenance.Overall,these findings suggest that molecular gradients serve as the organizing principle for maintaining the selection of sound frequencies by HCs.
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    RpL38 modulates germ cell differentiation by controlling Bam expression in Drosophila testis

    Yang FangFengchao ZhangFangzhen ZhaoJiajia Wang...
    2411-2425页
    查看更多>>摘要：Switching from mitotic spermatogonia to meiotic spermatocytes is critical to producing haploid sperms during male germ cell differ-entiation.However,the underlying mechanisms of this switch remain largely unexplored.In Drosophila melanogaster,the gene RpL38 encodes the ribosomal protein L38,one component of the 60S subunit of ribosomes.We found that its depletion in spermatogonia severely diminished the production of mature sperms and thus led to the infertility of male flies.By examining the germ cell differentiation in testes,we found that RpL38-knockdown blocked the transition from spermatogonia to spermatocytes and accumulated spermatogonia in the testis.To understand the intrinsic reason for this blockage,we conducted proteomic analysis for these spermatogonia populations.Differing from the control spermatogonia,the accumulated spermatogonia in RpL38-knockdown testes already expressed many spermatocyte markers but lacked many meiosis-related proteins,suggesting that spermatogonia need to prepare some important proteins for meiosis to complete their switch into spermatocytes.Mechanistically,we found that the expression of bag of marbles(bam),a crucial determinant in the transition from spermatogonia to spermatocytes,was inhibited at both the mRNA and protein levels upon RpL38 depletion.We also confirmed that the bam loss phenocopied RpL38 RNAi in the testis phenotype and transcriptomic profiling.Strikingly,overexpressing bam was able to fully rescue the testis abnormality and infertility of RpL38-knockdown flies,indicating that bam is the key effector downstream of RpL38 to regulate spermatogonia differentiation.Overall,our data suggested that germ cells start to prepare meiosis-related proteins as early as the spermatogonial stage,and RpL38 in spermatogonia is required to regulate their transition toward spermatocytes in a bam-dependent manner,providing new knowledge for our understanding of the transition process from spermatogonia to spermatocytes in Drosophila spermatogenesis.
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    Temperature regulates negative supercoils to modulate meiotic crossovers and chromosome organization

    Yingjin TanTaicong TanShuxian ZhangBo Li...
    2426-2443页
    查看更多>>摘要：Crossover recombination is a hallmark of meiosis that holds the paternal and maternal chromosomes(homologs)together for their faithful segregation,while promoting genetic diversity of the progeny.The pattern of crossover is mainly controlled by the architecture of the meiotic chromosomes.Environmental factors,especially temperature,also play an important role in modulating crossovers.However,it is unclear how temperature affects crossovers.Here,we examined the distribution of budding yeast axis components(Red1,Hop1,and Rec8)and the crossover-associated Zip3 foci in detail at different temperatures,and found that both increased and decreased temperatures result in shorter meiotic chromosome axes and more crossovers.Further investigations showed that temperature changes coordinately enhanced the hyperabundant accumulation of Hop1 and Red1 on chromosomes and the number of Zip3 foci.Most importantly,temperature-induced changes in the distribution of axis proteins and Zip3 foci depend on changes in DNA negative supercoils.These results suggest that yeast meiosis senses temperature changes by increasing the level of negative supercoils to increase crossovers and modulate chromosome organization.These findings provide a new perspective on understanding the effect and mechanism of temperature on meiotic re-combination and chromosome organization,with important implications for evolution and breeding.
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