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| 1 | Generation and characterization of stable pig pregastrulation epiblast stem cell lines显示文摘Pig epiblast-derived pluripotent stem cells are considered to have great potential and broad prospects for human therapeutic model developme nt and livestock breeding.Despite on going attempts since the 1990s,no stably defined pig epiblast-derived stem cell line has bee n established.Here,guided by in sights from a large-scale sin gle-cell tran scriptome an alysis of pig embryos from embryonic day(E)0 to E14,specifically,the tracing of pluripotency changes during epiblast development,we developed an in vitro culture medium for establishing and maintaining stable pluripotent stem cell lines from pig E10 pregastrulation epiblasts(pgEpiSCs).Enabled by chemical inhibition of WNT-related signaling in combination with growth factors in the FGF/ERK,JAK/STAT3,and Activin/Nodal pathways,pgEpiSCs maintain their pluripotency transcriptome features,similar to those of E10 epiblast cells,and normal karyotypes after more than 240 passages and have the potential to differentiate into three germ layers.Strikingly,ultradeep in situ Hi-C analysis revealed functional impacts of chromatin 3D-spatial associations on the transcriptional regulation of pluripote ncy marker genes in pgEpiSCs.I n practice,we con firmed that pgEpiSCs readily tolerate at least three rounds of successive gene editi ng and gene rated cloned gen e-edited live piglets.Our findings deliver on the long-a nticipated promise of pig pluripote nt stem cells and open new avenues for biological research,animal husbandry,and regenerative biomedicine. | Minglei Zhi Jinying Zhang Qianzi Tang Dawei Yu Shuai Gao Dengfeng Gao Pengliang Liu Jianxiong Guo Tang Hai Jie Gao Suying Cao Zimo Zhao Chongyang Li Xiaogang Weng Mengnan He Tianzhi Chen Yingjie Wang Keren Long Deling Jiao Guanglei Li Jiaman Zhang Yan Liu Yu Lin Daxin Pang Qianqian Zhu Naixin Chen Jingjing Huang Xinze Chen Yixuan Yao Jingcang Yang Zicong Xie Xianya Huang Mengxin Liu Ran Zhang Qiuyan Li Yiliang Miao Jianhui Tian Xingxu Huang Hongsheng Ouyang Bofeng Liu Wei Xie Qi Zhou Zhonghua Liu Caihong Zheng Mingzhou Li Jianyong Han | 2022 | Cell Research2022，32，4： | 3 |
| 2 | The Transcription Factor PLZF Directs the Effector Program of the NKT Cell Lineage显示文摘 | Adam K. Savage Michael G. Constantinides Jin Han Damien Picard Emmanuel Martin Bofeng Li Olivier Lantz Albert Bendelac | 2008 | Immunity2008，，3： | 1 |
| 3 | Generation of inactivated IL2RG and RAG1 monkeys with severe combined immunodeficiency using base editing显示文摘Severe combined immunodeficiency(SCiD)encompasses a range of inherited disorders that lead to a profound deterioration of the immune system.Among the pivotal genes associated with SCID,RAG1 and IL2RG play crucial roles.IL2RG is essential for the development,differentiation,and functioning of T,B,and NK cells,while RAG1 critically contributes to adaptive immunity by facilitating V(D)J recombination during the maturation of lymphocytes.Animal models carrying mutations in these genes exhibit notable deficiencies in their immune systems. | Xiao Zheng Chunhui Huang Yingqi Lin Bofeng Han Yizhi Chen Caijuan Li Jiawei Li Yongyan Ding Xichen Song Wei Wang Weien Liang Jianhao Wu Jiaxi Wu Jiale Gao Chengxi Wei Xudong Zhang Zhuchi Tu Sen Yan | 2023 | Signal Transduction and Targeted Therapy2023，8，10： | 0 |
| 4 | Tauopathy promotes spinal cord-dependent production of toxic amyloid-beta in transgenic monkeys显示文摘Tauopathy,characterized by the hyperphosphorylation and accumulation of the microtubule-associated protein tau,and the accumulation of Aβ oligomers,constitute the major pathological hallmarks of Alzheimer's disease.However,the relationship and causal roles of these two pathological changes in neurodegeneration remain to be defined,even though they occur together or independently in several neurodegenerative diseases associated with cognitive and movement impairment. | Zhuchi Tu Sen Yan Bofeng Han Cajuan Li Weien Liang Yingqi Lin Yongyan Ding Huiyi Wei Lu Wang Hao Xu Jianmeng Ye Bang Li Shihua Li Xiao-Jiang Li | 2023 | Signal Transduction and Targeted Therapy2023，8，10： | 0 |
| 5 | Large animal models for Huntington's disease research显示文摘Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders. | Bofeng Han Weien Liang Xiao-Jiang Li Shihua Li Sen Yan Zhuchi Tu | 2024 | Zoological Research2024，45，2： | 0 |
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