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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 | Interleukin 1 beta-induced chloride currents are important in osteoarthritis onset:an in vitro study显示文摘Persistent hypotonic and inflammatory conditions in the joint cavity can lead to the loss of cartilage matrix and cell death,which are the important mechanisms of osteoarthritis(OA)onset.Previous studies have confirmed that the existence of a hypotonic environment is a red flag for inflammation,as hypotonic environment induces the opening of the chloride channel of the cell and promotes chloride ion efflux,which prompts the cell volume to increase.Chloride channels play an important role in the regulation of mineralization and chondrocyte death.Here,we reported that OA chondrocytes showed a significant increase of cell death rate and the imbalance of cartilage matrix catabolism.We found that the distribution of skeleton protein F-actin was disordered.In addition,the volume-sensitive chloride current of OA chondrocytes decreased significantly with the increase of the expression levels of inflammation-related proteins caspase-1,caspase-3,and NLRP3.Moreover,interleukin-1β(IL-1β)showed a potential to activate the chloride current of normal chondrocytes.These results indicate that IL-1β-induced chloride channel opening in chondrocytes may be closely related to the occurrence of OA.This chloride channel opening process may therefore be a potential target for the treatment of OA. | Zhiqin Deng Zicong Lin Qing Zhong Minqiang Lu Huankun Fang Jianquan Liu Li Duan Lixin Chen Liwei Wang Daping Wang Wencui Li | 2021 | Acta Biochimica et Biophysica Sinica2021，53，4： | 2 |
| 3 | Decoding Cortical Glial Cell Development显示文摘Mouse cortical radial glial cells(RGCs)are primary neural stem cells that give rise to cortical oligodendrocytes,astrocytes,and olfactory bulb(OB)GABAergic interneurons in late embryogenesis.There are fundamental gaps in understanding how these diverse cell subtypes are generated.Here,by combining single-cell RNA-Seq with intersectional lineage analyses,we show that beginning at around E16.5,neocortical RGCs start to generate ASCL1^(+)EGFR^(+)apical multipotent intermediate progenitors(MIPCs),which then differentiate into basal MIPCs that express ASCL1,EGFR,OLIG2,and MKI67.These basal MIPCs undergo several rounds of divisions to generate most of the cortical oligodendrocytes and astrocytes and a subpopulation of OB interneurons.Finally,single-cell ATAC-Seq supported our model for the genetic logic underlying the specification and differentiation of cortical glial cells and OB interneurons.Taken together,this work reveals the process of cortical radial glial cell lineage progression and the developmental origins of cortical astrocytes and oligodendrocytes. | Xiaosu Li Guoping Liu Lin Yang Zhenmeiyu Li Zhuangzhi Zhang Zhejun Xu Yuqun Cai Heng Du Zihao Su Ziwu Wang Yangyang Duan Haotian Chen Zicong Shang Yan You Qi Zhang Miao He Bin Chen Zhengang Yang | 2021 | Neuroscience Bulletin2021，37，4： | 2 |
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