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| 1 | One-step generation of p53 gene biallelic mutant Cynomolgus monkey via the CRISPR/Cas system显示文摘 | Haifeng Wan Chunjing Feng Fei Teng Shihua Yang Baoyang Hu Yuyu Niu Andy Peng Xiang Weizhen Fang Weizhi Ji Wei Li Xiaoyang Zhao Qi Zhou | 2015 | Cell Research2015，25，2： | 39 |
| 2 | Generation of a precise Oct4-hrGFP knockin cynomolgus monkey model via CRISPR/Cas9-assisted homologous recombination显示文摘 | Yiqiang Cui Yuyu Niu Jiankui Zhou Yongchang Chen Yiwei Cheng Shangang Li Zongyong Ai Chu Chu Hong Wang Bo Zheng Xuejin Chen Jiahao Sha Xuejiang Guo Xingxu Huang Weizhi Ji | 2018 | Cell Research2018，28，3： | 13 |
| 3 | Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development显示文摘Brain size and cognitive skills are the most dramatically changed traits in humans during evolution and yet the genetic mechanisms underlying these human-specific changes remain elusive.Here,we successfully generated 11 transgenic rhesus monkeys(8 first-generation and 3 second-generation)carrying human copies of MCPH1,an important gene for brain development and brain evolution.Brain-image and tissue-section analyses indicated an altered pattern of neural-cell differentiation,resulting in a delayed neuronal maturation and neural-fiber myelination of the transgenic monkeys,similar to the known evolutionary change of developmental delay(neoteny)in humans.Further brain-transcriptome and tissue-section analyses of major developmental stages showed a marked human-like expression delay of neuron differentiation and synaptic-signaling genes,providing a molecular explanation for the observed brain-developmental delay of the transgenic monkeys.More importantly,the transgenic monkeys exhibited better short-term memory and shorter reaction time compared with the wild-type controls in the delayed-matching-to-sample task.The presented data represent the first attempt to experimentally interrogate the genetic basis of human brain origin using a transgenic monkey model and it values the use of non-human primates in understanding unique human traits. | Lei Shi Xin Luo Jin Jiang Yongchang chen Cirong Liu Ting Hu Min Li Qiang Lin Yanjiao Li Jun Huang Hong Wang Yuyu Niu Yundi Shi Martin Styner Jianhong Wang Yi Lu Xuejin Sun Hualin Yu Weizhi Ji Bing Su | 2019 | National Science Review2019，6，3： | 12 |
| 4 | Generation of a Hutchinson-Gilford progeria syndrome monkey model by base editing显示文摘Many human genetic diseases,including Hutchinson-Gilford progeria syndrome(HGPS),are caused by single point mutations.HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene.Base editors(BEs)composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions.Here,we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA(gRNA)targeting the LMNA gene via microinjection into monkey zygotes.Five out of six newborn monkeys carried the mutation specifically at the target site.HGPS monkeys expressed the toxic form of lamin A,progerin,and recapitulated the typical HGPS phenotypes including growth retardation,bone alterations,and vascular abnormalities.Thus,this monkey model genetically and clinically mimics HGPS in humans,demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates. | Fang Wang Weiqi Zhang Qiaoyan Yang Yu Kang Yanling Fan Jingkuan Wei Zunpeng Liu Shaoxing Dai Hao Li Zifan Li Lizhu Xu Chu Chu Jing Qu Chenyang Si Weizhi Ji Guang-Hui Liu Chengzu Long Yuyu Niu | 2020 | Protein & Cell2020，11，11： | 11 |
| 5 | Identification and characterization of an ancient class of small RNAs enriched in serum associating with active infection显示文摘 | Yunfang Zhang Ying Zhang Junchao Shi He Zhang Zhonghong Cao Xuan Gao Wanhua Ren Yunna Ning Lina Ning Yujing Cao Yongchang Chen Weizhi Ji Zi-jiang Chen Qi Chen Enkui Duan | 2014 | Journal of Molecular Cell Biology2014，8，2： | 10 |
| 6 | Genome editing in large animals: current status and future prospects显示文摘Large animals(non-human primates,livestock and dogs)are playing important roles in biomedical research,and large livestock animals serve as important sources of meat and milk.The recently developed programmable DNA nucleases have revolutionized the generation of gene-modified large animals that are used for biological and biomedical research.In this review,we briefly introduce the recent advances in nuclease-meditated gene editing tools,and we outline these editing tools’applications in human disease modeling,regenerative medicine and agriculture.Additionally,we provide perspectives regarding the challenges and prospects of the new genome editing technology. | Jianguo Zhao Liangxue Lai Weizhi Ji Qi Zhou | 2019 | National Science Review2019，6，3： | 10 |
| 7 | Germline acquisition of Cas9/RNA-mediated gene modifications in monkeys显示文摘 | Yongchang Chen Yiqiang Cui Bin Shen Yuyu Niu Xiaoyang Zhao Lei Wang Jianying Wang Wei Li Qi Zhou Weizhi Ji Jiahao Sha Xingxu Huang | 2015 | Cell Research2015，25，2： | 8 |
| 8 | Transgenic Nonhuman Primate Models for Human Diseases:Approaches and Contributing Factors显示文摘非人类的首领(NHP ) 提供有力的试验性的模型学习人的开发,认知功能和骚乱以及复杂行为,因为他们到人的基因、生理的类似。因此, NHP 是为人的疾病的学习的适当模型,例如包括 Parkinson 的, Alzheimer 的并且亨廷顿的疾病的 neurodegenerative 疾病,它由于基因变化发生。然而,折磨人的如此的疾病不在 NHP 自然地发生。那么转基因的 NHP 需要被证实理解疾病病理和致病的病原学。把基因模型,比作啮齿类动物为人的疾病的转基因的 NHP 的产生是低效的,并且为亨廷顿的疾病的一个仅仅转基因的猴子模型被报导了。这评论为产生转基因的 NHP 学习人的疾病集中于潜在的途径和作出贡献的因素。 | Yongchang Chen | 2012 | Journal of Genetics and Genomics2012，39，6： | 5 |
| 9 | Netrin-1 signaling mediates NO-induced glial precursor migration and accumulation显示文摘 | Hongwei Chen Qiang Wei Jing Zhang Chuankun Xu Tao Tan Weizhi Ji | 2010 | Cell Research2010，20，2： | 3 |
| 10 | Paving the road for biomedicine: genome editing and stem cells in primates显示文摘Non-human primates(NHPs) are similar with humans in their anatomy, physiology, genetics and neural functions, and in their cognition, emotions and social behavior. The NHP model has played an important role in the biomedical research, development of vaccines and drugs and new therapies for many diseases.Recent advances in genome editing have generated NHP models for human diseases. Genome editing integrated with derivation of NHP pluripotent stem cells now provides an optimal resource to regenerate medicine. | Yuyu Niu Tianqing Li Weizhi Ji | 2017 | National Science Review2017，4，4： | 3 |
| 11 | Isolation and characterization of liver epithelial progenitor cells from normal adult rhesus monkeys (Macaca mulatta)显示文摘 | Lifang Jin Shaohui Ji Xianghui Tang Xiangyu Guo Yongqing Lu Hongwei Chen Hongkui Deng Qi Zhou Weizhi Ji | 2009 | Cell Research2009，19，2： | 2 |
| 12 | Cross-species single-cell transcriptomic analysis reveals divergence of cell composition and functions in mammalian ileum epithelium显示文摘Animal models are widely used for biomedical studies and drug evaluation.The small intestine plays key roles in nutrient absorption,hormone secretion,microbiota defense and drug absorption and metabolism.Although the intestinal structure of mammals is conserved,the differences on epithelial cell composition,functional assignments and drug absorption among mammals are largely unknown.Here,cross-species analysis of single-cell transcriptomic atlas of the ileum epithelium from mouse,rat,pig,macaque and human reveals the conserved and differential cell types and functions among species,identifies a new CA7+cell type in pig,macaque and human ileum,uncovers the distinct expression pattern in enterocytes,enteroendocrine cells and Paneth cells,and defines the conserved and species-specific intestinal stem cell signature genes.The examination of drug absorption across species suggests that drug metabolism in mouse ileum is closer to human while drug transport in macaque ileum is more similar to human.Together,our data provide the comprehensive information about cell composition and functional assignments in five species,and offer the valuable guidance for animal model selection and drug testing. | Haonan Li Xiaodan Wang Yalong Wang Mengxian Zhang Fan Hong Hong Wang Along Cui Jianguo Zhao Weizhi Ji Ye-Guang Chen | 2022 | Cell Regeneration2022，11，1： | 2 |
| 13 | C1orf106, an innate immunity activator, is amplified in breast cancer and is required for basal-like/luminal progenitor fate decision显示文摘Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other subtypes.However,genes that specifically promote basal-like breast cancer development remain largely unknown.Here,we report that a novel gene C1orf106 plays an important role in maintaining the feature of basal-like/luminal progenitors.C1orf106 is frequently amplified and overexpressed in basal-like breast cancer and is associated with a poor outcome in patients.In human TCGA database,C1orf106 expression was correlated with upregulation of ELF5 and downregulation of GATA3,two transcription factors that regulate mammary gland stem cell fate.Enhanced expression of C1orf106 promotes tumor progression and expression of basal-like/luminal progenitor marker ELF5;depletion of C1orf106 suppresses tumorigenesis and expression of basal-like/luminal progenitor marker GATA3.These findings suggest that C1orf106 maintains the basal-like/luminal progenitor character through balancing the expression of ELF5 and GATA3.Taken together,we demonstrated that C1orf106 is an important regulator for basal-like/luminal progenitors and targeting C1orf106 is of therapeutic value for breast cancer. | Ji Ma Cheng Liu Decao Yang Jiagui Song Jing Zhang Tianzhuo Wang Mengyuan Wang Weizhi Xu Xueying Li Shigang Ding Jun Zhan Hongquan Zhang | 2019 | Science China(Life Sciences)2019，62，9： | 2 |
| 14 | Primate stem cells: bridge the translation from basic research to clinic application显示文摘A growing body of literature has shown that stem cells are very effective for the treatment of degenerative diseases in rodents but these exciting results have not translated to clinical practice. The difference results from the divergence in genetic, metabolic, and physiological phenotypes between rodents and humans. The high degree of similarity between non-human primates(NHPs) and humans provides the most accurate models for preclinical studies of stem cell therapy. Using a NHP model to understand the following key issues, which cannot be addressed in humans or rodents, will be helpful for extending stem cell applications in the basic science and the clinic. These issues include pluripotency of primate stem cells, the safety and efficiency of stem cell therapy, and transplantation procedures of stem cells suitable for clinical translation. Here we review studies of the above issues in NHPs and current challenges of stem cell applications in both basic science and clinical therapies. We propose that the use of NHP models, in particular combining the serial production and transplantation procedures of stem cells is the most useful for preclinical studies designed to overcome these challenges. | Tianqing Li Zongyong Ai Weizhi Ji | 2019 | Science China(Life Sciences)2019，62，1： | 2 |
| 15 | Transcriptome dynamics of hippocampal neurogenesis in macaques across the lifespan and aged humans显示文摘Whether adult hippocampal neurogenesis(AHN)persists in adult and aged humans continues to be extensively debated.A major question is whether the markers identified in rodents are reliable enough to reveal new neurons and the neurogenic trajectory in primates.Here,to provide a better understanding of AHN in primates and to reveal more novel markers for distinct cell types,droplet-based single-nucleus RNA sequencing(snRNA-seq)is used to investigate the cellular heterogeneity and molecular characteristics of the hippocampi in macaques across the lifespan and in aged humans.All of the major cell types in the hippocampus and their expression profiles were identified.The dynamics of the neurogenic lineage was revealed and the diversity of astrocytes and microglia was delineated.In the neurogenic lineage,the regulatory continuum from adult neural stem cells(NSCs)to immature and mature granule cells was investigated.A group of primate-specific markers were identified.We validated ETNPPL as a primate-specific NSC marker and verified STMN1 and STMN2 as immature neuron markers in primates.Furthermore,we illustrate a cluster of active astrocytes and microglia exhibiting proinflammatory responses in aged samples.The interaction analysis and the comparative investigation on published datasets and ours imply that astrocytes provide signals inducing the proliferation,quiescence and inflammation of adult NSCs at different stages and that the proinflammatory status of astrocytes probably contributes to the decrease and variability of AHN in adults and elderly individuals. | Wei Wang Mengdi Wang Meng Yang Bo Zeng Wenying Qiu Qiang Ma Xiaoxi Jing Qianqian Zhang Bosong Wang Chonghai Yin Jiyao Zhang Yuxin Ge Yufeng Lu Weizhi Ji Qian Wu Chao Ma Xiaoqun Wang | 2022 | Cell Research2022，32，8： | 2 |
| 16 | Establishment of porcine and monkey colonic organoids for drug toxicity study显示文摘Pig and monkey are widely used models for exploration of human diseases and evaluation of drug efficiency and toxicity,but high cost limits their uses.Organoids have been shown to be promising models for drug test as they reasonably preserve tissue structure and functions.However,colonic organoids of pig and monkey are not yet established.Here,we report a culture medium to support the growth of porcine and monkey colonic organoids.Wnt signaling and PGE2 are important for long-term expansion of the organoids,and their withdrawal results in lineage differentiation to mature cells.Furthermore,we observe that porcine colonic organoids are closer to human colonic organoids in terms of drug toxicity response.Successful establishment of porcine and monkey colonic organoids would facilitate the mechanistic investigation of the homeostatic regulation of the intestine of these animals and is useful for drug development and toxicity studies. | Haonan Li Yalong Wang Mengxian Zhang Hong Wang Along Cui Jianguo Zhao Weizhi Ji Ye-Guang Chen | 2021 | Cell Regeneration2021，10，1： | 1 |
| 17 | Establishment of customized mouse stem cell lines by sequential nuclear transfer显示文摘治疗学的克隆,胚胎的干细胞(转换字符) 由此从原子转移(NT ) 被导出胚胎,可以在再生药的新时代起一个主要作用。Inthis 学习我们建立了四十原子转移 -- 从不同施主房间类型或段落的 NTembryos 被导出的转换字符(NT 转换字符) 线。我们发现 NT 转换字符能够形成胚胎植物或动物身体。另外, NT 转换字符表示了 pluripotency 干细胞标记试管内并且能区分进胚胎的纸巾体内。从施主房间能形成完整的术语的早经过 R1 的 NT 胚胎开发了小狗,而那些为为实时出生是必要的 reprogramming 从迟了的经过 R1 ES 施主房间失去了潜力。我们随后建立了近来从 NT 胚囊被开发的 sequentialNT-R1-ESC 线经过 R1 转换字符施主。然而,当在他们的早段落用作原子转移施主时,这些 NT-R1-ESC 排队,没能导致实时小狗。这显示用顺序的 NT 转换字符的治疗学的克隆过程不能救居住在以前的施主代的发展缺乏。 | Chunli Zhao Ruqiang Yao Jie Hao Chenhui Ding Yong Fan Xiangpeng Dai Wei Li Tang Hai Zichuan Liu Yang Yu Yingying Wang Xiaojun Hou Weizhi Ji Qi Zhou Alice Jouneau Fanyi Zeng Liu Wang | 2007 | Cell Research2007，17，1： | 1 |
| 18 | Characterization of an antiproliferative exopolysaccharide(LHEPS-2)from Lactobacillus helveticus MB2-1显示文摘 | LI Wei JI Juan TANG Weizhi | 2014 | Carbohydrate Polymers2014，105，： | 1 |
| 19 | Conjugated polymer-controlled selective dispersion of single-walled carbon nanotubes and fabrication of network transistors显示文摘 | LingLi Zhang Han Wang Moyun Chen Ji Ma Weizhi Wang | 2013 | Macromolecular Research2013，，10： | 1 |
| 20 | De novo DNA methylation during monkey pre-implantation embryogenesis显示文摘首领 embryogenesis 的批评 epigenetic 规定必要 DNA methylome 变化。这里,我们在培植前恒河猴胚胎以及用定序方法的优化基于 tagmentation 的整个染色体的重亚硫酸盐学习的男、女的配偶子报导 DNA methylation 的染色体宽的作文, patterning,和阶段特定的动力学。我们证明在授精之上,父亲、母亲的染色体经历活跃 DNA demethylation,和染色体宽的 de novo DNA methylation 也在一样的时期被开始。由 8 房间阶段, remethylation 变得比 demethylation 更显著,导致全球 DNA methylation 的增加。基因的倡导者与氧化 phosphorylation 联系了,建议精力新陈代谢的这个模式不能被赞成是优先地在 8 房间阶段的 remethylated。在啮齿类动物不同, X 染色体 inactivation 没在猴子培植前开发期间被观察。我们的学习提供蜡的第一幅全面插图并且衰退 DNA methylation 动力学的阶段。最重要地,我们的 DNA methyltransferase loss-of-function 分析显示 DNA methylation 影响早猴子 embryogenesis。 | Fei Gao Yuyu Niu Yi Eve Sun Hanhn Lu Yongchang Chen Siguang Li Yu Kang Yuping Luo Chenyang Ni Juehua Yu Chang Li Nianqin Sun Wei Si Hong Wang Weizhi Ji Tao Tan | 2017 | Cell Research2017，27，4： | 1 |
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