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| 1 | AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells显示文摘The current coronavirus disease 2019(COVID-19)pandemic presents a global public health challenge.The viral pathogen responsible,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),binds to the host receptor ACE2 through its spike(S)glycoprotein,which mediates membrane fusion and viral entry.Although the role of ACE2 as a receptor for SARS-CoV-2 is clear,studies have shown that ACE2 expression is extremely low in various human tissues,especially in the respiratory tract.Thus,other host receptors and/or co-receptors that promote the entry of SARS-CoV-2 into cells of the respiratory system may exist.In this study,we found that the tyrosine-protein kinase receptor UFO(AXL)specifically interacts with the N-terminal domain of SARS-CoV-2 S.Using both a SARS-CoV-2 virus pseudotype and authentic SARS-CoV-2,we found that overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry as efficiently as overexpression of ACE2,while knocking out AXL significantly reduces SARS-CoV-2 infection in HI 299 pulmonary cells and in human primary lung epithelial cells.Soluble human recombinant AXL blocks SARS-CoV-2 infection in cells expressing high levels of AXL.The AXL expression level is well correlated with SARS-CoV-2 S level in bronchoalveolar lavage fluid cells from COVID-19 patients.Taken together,our findings suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role in promoting viral infection of the human respiratory system and indicate that it is a potential target for future clinical intervention strategies. | Shuai Wang Zongyang Qiu Yingnan Hou Xiya Deng Wei Xu Tingting Zheng Peihan Wu Shaofang Xie Weixiang Bian Chong Zhang Zewei Sun Kunpeng Liu Chao Shan Aifu Lin Shibo Jiang Youhua Xie Qiang Zhou Lu Lu Jing Huang Xu Li | 2021 | Cell Research2021，31，2： | 39 |
| 2 | Multiple sgRNAs facilitate base editingmediated i-stop to induce complete and precise gene disruption显示文摘Dear Editor,Gene editing is a process to introduce desired changes into targeted loci of genomic DNA.Recently,type II clustered regularly in terspaced short palindromic repeats-associated Cas9 endonuclease(CRISPR/Cas9)system has been demonstrated as a versatile tool for engineering eukaryote genome(Hsu et al.,2014),such as in mice(Zuo et al.,2017). | Kun Jia Zongyang Lu Fei Zhou Zhiqi Xiong Rui Zhang Zhiwei Liu Yu'e Ma Lei He Cong Li Zhen Zhu Dejing Pan Zhengxing Lian | 2019 | Protein & Cell2019，10，11： | 3 |
| 3 | Generation of isogenic single and multiplex gene knockout mice by base editing-induced STOP显示文摘Although CRISPR/Cas9 has been widely used to generate knockout mice, two major limitations remain:the founders usually carry a mixture of genotypes, and mosaicism harboring multiple genotypes.Therefore, it takes a long time to get homozygous mutants. Recently developed base editing(BE) system,which introduces C-to-T conversion without double strand DNA cleavage, has been used to introduce artificial stop codons(i-STOP) to prematurely terminate translation, providing a cleaner strategy for genome engineering. Using this strategy, we generated CD160 KO and VISTA/CD160 double KO mice by microinjection of a single sg RNA targeting CD160 and a mixture of sg RNAs targeting VISTA and CD160,respectively. The BE system induced STOP efficiently in mouse embryos and consequently in founder mice without detectable off-target. Most interestingly, the majority of the mutants harbor same genetic modifications, indicating we generated isogenic single and multiplex gene mutant mice by BE-induced STOP. We also obtained homozygous mutant mouse in F1 mice, demonstrating the accelerated strategy in generating animal models. | Guang Yang Tianyu Zhu Zongyang Lu Guanglei Li Hao Zhang Songjie Feng Yajing Liu Jianan Li Yu Zhang Jia Chen Xuejiang Guo Xingxu Huang | 2018 | Science Bulletin2018，63，17： | 2 |
| 4 | Allele-specific genome editing of imprinting genes by preferentially targeting non-methylated loci using Staphylococcus aureus Cas9(SaCas9)显示文摘Allele-specific DNA methylation is the most important imprinting marker localized to differentially methylated regions(DMRs),and aberrant genomic imprinted DNA methylation is associated with some human diseases,including Prader-Willi syndrome and cancer.Thus,the development of an effective strategy for the precise editing of allele-specific methylated genes is essential for the functional clarification of imprinting elements and the correction of imprinting disorders in human diseases.To discover a feasible allele-specific genome editing tool based on the CRISPR/Cas system,which is an efficient genetargeting technique in various organisms,we examined the targeting efficiency of Staphylococcus aureus Cas9(SaCas9)and Streptococcus pyogenes Cas9(SpCas9)in response to DNA methylation interference.We found that the targeting efficiency of SaCas9,but not SpCas9,was enhanced by targeted DNA demethylation using the d Cas9-Tet1 catalytic domain(CD)but suppressed by targeted DNA methylation using Dnmt3l-Dnmt3a-d Cas9.An in vitro cleavage assay further demonstrated that SaCas9 nuclease activity was inhibited by 5-methylcytosine(5mC)in a synthesized Cp G-containing context.Further analysis with Ch IP-Q-PCR demonstrated that the non-methylated sequence targeting of Sa Cas9 depends on the binding preference of SaCas9 to non-methylated sequences.Taking advantage of this feature of SaCas9,we have successfully obtained non-methylated allele-biased targeted embryos/mice for two imprinting genes,H19 and Snrpn,with relatively high efficiencies of 28.6%and 47.4%,respectively.These results indicate that the targeting efficiency of SaCas9 was strongly reduced by DNA methylation.By using SaCas9,we successfully achieved allele-specific genome editing of imprinting genes by preferentially targeting non-methylated loci. | Yajing Liu Jianan Li Changyang Zhou Bin Meng Yu Wei Guang Yang Zongyang Lu Qingmei Shen Yu Zhang Hui Yang Yunbo Qiao | 2019 | Science Bulletin2019，64，21： | 1 |
| 5 | Cynomolgus-rhesus hybrid macaques serve as a platform for imprinting studies显示文摘Genomic imprinting can lead to allele-specific expression(ASE),where one allele is preferentially expressed more than the other.Perturbations in genomic imprinting or ASE genes have been widely observed across various neurological disorders,notably autism spectrum disorder(ASD).In this study,we crossed rhesus cynomolgus monkeys to produce hybrid monkeys and established a framework to evaluate their allele-specific gene expression patterns using the parental genomes as a reference.Our proof-of-concept analysis of the hybrid monkeys identified 353 genes with allele-biased expression in the brain,enabling us to determine the chromosomal locations of ASE clusters.Importantly,we confirmed a significant enrichment of ASE genes associated with neuropsychiatric disorders,including ASD,highlighting the potential of hybrid monkey models in advancing our understanding of genomic imprinting. | Zongyang Lu Jie Li Yong Lu Ling Li Wei Wang Chenchen Zhang Libing Xu Yanhong Nie Changshan Gao Xinyan Bian Zhen Liu Guang-Zhong Wang Qiang Sun | 2023 | The Innovation2023，4，3： | 0 |
| 6 | Phenomenology of heavy neutral gauge boson at muon collider显示文摘Heavy neutral gauge boson Z' is proposed in many new physics models.It has rich phenomena at the future muon collider.We study the properties of Z' boson with the process of μ^(+)μ^(-)→qq,μ^(+)μ^(-)→l^(+)l^(-),μ^(+)μ^(-)→ ZH and μ^(+)μ^(-)→ W^(+)W^(-).The discrepancy of Z' coupling to different types of particles can be shown in the cross section distributions around the resonance peak of various decay modes.Angular distributions of the final quark or lepton in μ^(+)μ^(-)→qq/l^(+)l^(-)process are sensitive to the parameters such as mass of Z' and the Z-Z' mixing angle.The interaction of new gauge boson coupling to the standard model gauge particles and Higgs boson are also studied through μ^(+)μ^(-)→ ZH→l^(+)l^(-)bb and μ^(+)u^(-)→ W^(+)W^(-)→l^(+)l^(-)v_(l)v_(l).The cross section and the final particles' angular distributions with the contribution of Z' boson differ from those processes with only standard model particles.A forward-backward asymmetry defined by the angular distribution is provided to show the potential of searching for new physics at the muon collider.Especially,the beam polarization with certain value can effectively enlarge the forward-backward asymmetry. | Zongyang Lu Honglei Li Zhi-Long Han Zong-Guo Si Liuxin Zhao | 2024 | Science China(Physics,Mechanics & Astronomy)2024，67，3： | 0 |
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