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Deciphering the placental abnormalities associated with somatic cell nuclear transfer at single-nucleus resolution

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Protein & Cell 2023年第12期14卷 924-928页

作者： Liyuan Jiang Xin Wang Leyun Wang Sinan Ma Yali Ding Chao Liu Siqi Wang Xuan Shao Ying Zhang Zhikun Li Wei Li guihai feng Qi Zhou College of Life Sciences Northeast Agricultural UniversityHarbin 150030China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regenerative Medicine Chinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China

Dear Editor,The placenta connecting the fetus to the matermal uterus provides material exchange and an immune-tolerant environment for the embryo in all eutherian mammals(Shao et al.,2022).The representative mouse placenta displays a multilayered structure with distinct characteristics and functions,including the matermal decidua,junctional zone,and labyrinth layer(Marsh and Blelloch,2020).The decidua,which is thought to be derived from the matermal endometrium(and further undergoes decidualization),provides an anchor for fetal trophoblast invasion.The junctional zone predominantly contains spongiotrophoblasts(SpT),glycogen trophoblasts(GlyT),and trophoblast giant cells(TGCs).The labyrinth is the innermost two-layer structure,which mainly consists of syncytiotrophoblast cells(SynTI and SynTII),sinusoidal TGCs(S-TGCs),and fetal endothelial cells(Simmons and Cross,2005).

关键词： fetal invasion fetus

Rapid construction of a whole-genome mutant library by combining haploid stem cells and inducible self-inactivating PiggyBac transposon

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Protein & Cell 2020年第6期11卷 452-457页

作者： Junjie Mao Kai Xu Jiabao Han guihai feng Ying Zhang Wei Li State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Dear Editor,Genome-scale screening is a powerful method used to explore phenotypes that are of interest,and numerous screening systems have been built for functional sites identification.Classical genetic screening in eukaryotes has been performed using chemical mutagens(Chen et al.,2000),transposon mediated gene trapping(Dupuy et al.,2005),and CRISPR-Cas9 system(Wang et al.,2014).

关键词： PiggyBac inducible inactivating

Lipid metabolism dysfunction induced by age-dependent DNA methylation accelerates aging

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Signal Transduction and Targeted Therapy 2022年第6期7卷 2105-2116页

作者： Xin Li Jiaqiang Wang LeYun Wang Yuanxu Gao guihai feng Gen Li Jun Zou Meixin Yu Yu Fei Li Chao Liu Xue Wei Yuan Ling Zhao Hong Ouyang Jian-Kang Zhu Wei Li Qi Zhou Kang Zhang State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of Sciences100101 BeijingChina Institute for Genomic Medicine University of California San DiegoLa JollaCA 92037USA Faculty of Medicine Macao University of Science and TechnologyTapaiMacao 999078China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyTapaiMacao 999078China Clinical Translational Innovation Center West China HospitalSichuan UniversityChengdu 610041China Guangzhou Women and Children Medical Center Guangzhou Medical UniversityGuangzhou 510623China Zhongshan Ophthalmic Center Sun Yat-sen UniversityGuangzhou 510060China Institute of Advanced Biotechnology and School of Life Sciences Southern University of Science and TechnologyShenzhen 518055China

Epigenetic alterations and metabolic dysfunction are two hallmarks of aging.However,the mechanism of how their interaction regulates aging,particularly in mammals,remains largely unknown.Here we show ELOVL fatty acid elongase 2(Elovl2),a gene whose epigenetic alterations are most highly correlated with age prediction,contributes to aging by regulating lipid metabolism.We applied artificial intelligence to predict the protein structure of ELOVL2 and the interaction with its substrate.Impaired Elovl2 function disturbs lipid synthesis with increased endoplasmic reticulum stress and mitochondrial dysfunction,leading to key aging phenotypes at both cellular and physiological level.Furthermore,restoration of mitochondrial activity can rescue age-related macular degeneration(AMD)phenotypes induced by Elovl2 deficiency in human retinal pigmental epithelial(RPE)cells;this indicates a conservative mechanism in both human and mouse.Taken together,we revealed an epigenetic-metabolism axis contributing to aging and illustrate the power of an AI-based approach in structure-function studies.

关键词： metabolism alterations dysfunction

MeCP2 deficiency promotes cell reprogramming by stimulating IGF1/AKT/mTOR signaling and activating ribosomal protein-mediated ceil cycle gene translation

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Journal of Molecular Cell Biology 2018年第6期10卷 515-526页

作者： Wei Zhang guihai feng Libin Wang Fei Teng Liu Wang Wei Li Ying Zhang Qi Zhou State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

The generation of induced pturipotent stem cells (iPSCs)offers a great opportunity in research and regenerative medicine.The current poor efficiency and incomplete mechanistic understanding of the reprogramming process hamper the clinical application of iPSCs. MeCP2 connects histone modification and DNA methyiation,which are key changes of somatic cell reprogramming.However,the rote of MeCP2 in celt reprogramming has not been examined.In this study,we found that MeCP2 deficiency enhanced reprogramming efficiency and stimulated cell proliferation through regulating cell cycle protein expression in the earLy stage of reprogramming.MeCP2 deficiency enhanced the expression of ribosomal protein genes,thereby enhancing reprogramming efficiency through promoting the translation of ceLl cycle genes.In the end,MeCP2 deficiency stimulated IGF1/AKT/mTOR signaling and activated ribosomal protein gene expression.Taken together,our data indicate that MeCP2 deficiency promoted cell reprogramming through stimulating IGF1/AKT/mTOR signaling and activating ribosomal protein-mediated cell cycle gene translation in the early stage of reprogramming.

关键词： MeCP2 cell reprogramming IGFI/AKT/mTOR signaling ribosomal protein cell cycle

Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs

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Protein & Cell 2020年第2期11卷 97-107页

作者： Rui Fu Dawei Yu Jilong Ren Chongyang Li Jing Wang guihai feng Xuepeng Wang Haifeng Wan Tianda Li Libin Wang Ying Zhang Tang Hai Wei Li Qi Zhou State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Blastocyst complementation by pluripotent stem cell(PSC)injection is believed to be the most promising method to generate xenogeneic organs.However,ethical issues prevent the study of human chimeras in the late embryonic stage of development.Primate embryonic stem cells(ESCs),which have similar pluripotency to human ESCs,are a good model for studying interspecies chimerism and organ generation.However,whether primate ESCs can be used in xenogenous grafts remains unclear.In this study,we evaluated the chimeric ability of cynomolgus monkey(Macaca fascicularis)ESCs(cmESCs)in pigs,which are excellent hosts because of their many similarities to humans.We report an optimized culture medium that enhanced the anti-apoptotic ability of cmESCs and improved the development of chimeric embryos,in which domesticated cmESCs(D-ESCs)injected into pig blastocysts differentiated into cells of all three germ layers.In addition,we obtained two neonatal interspecies chimeras,in which we observed tissue-specific D-ESC differentiation.Taken together,the results demonstrate the capability of D-ESCs to integrate and differentiate into functional cells in a porcine model,with a chimeric ratio of 0.001-0.0001 in different neonate tissues.We believe this work will facilitate future developments in xenogeneic organogenesis,bringing us one step closer to producing tissue-specific functional cells and organs in a large animal model through interspecies blastocyst complementation.

关键词： embryonic stem cells,blastocyst complementation cynomolgus monkey pig interspecies chimera organ reconstruction

Immunity-and-matrix-regulatory cells enhance cartilage regeneration for meniscus injuries: a phase I dose-escalation trial

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5873-5886页

作者： Liangjiang Huang Song Zhang Jun Wu Baojie Guo Tingting Gao Sayed Zulfiqar Ali Shah Bo Huang Yajie Li Bo Zhu Jiaqi Fan Liu Wang Yani Xiao Wenjing Liu Yao Tian Zhengyu Fang Yingying Lv Lingfeng Xie Sheng Yao Gaotan Ke Xiaolin Huang Ying Huang Yujuan Li Yi Jia Zhongwen Li guihai feng Yan Huo Wei Li Qi Zhou Jie Hao Baoyang Hu Hong Chen Department of Rehabilitation Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina National Stem Cell Resource Center State Key Laboratory of Stem Cell and Reproductive BiologyInstitute of ZoologyInstitute for Stem Cell and RegenerationChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Stem Cell Research Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina University of Chinese Academy of Sciences BeijingChina Beijing Key Lab for Pre-clinical Safety Evaluation of Drugs National Center for Safety Evaluation of DrugsNational Institutes for Food and Drug ControlBeijingChina Beijing Zephyrm Biotechnologies Co. Ltd.BeijingChina

Immunity-and-matrix-regulatory cells(IMRCs)derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix,which could be mass-produced with stable biological properties.Despite resemblance to mesenchymal stem cells(MSCs)in terms of self-renew and tri-lineage differentiation,the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined.Here,we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury.Following injection into the knees of rabbits with meniscal injury,IMRCs enhanced endogenous fibrocartilage regeneration.In the dose-escalating phase I clinical trial(NCT03839238)with eighteen patients recruited,we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting.Furthermore,the effective results of magnetic resonance imaging(MRI)of meniscus repair and knee functional scores suggested that 5×107 cells are optimal for meniscus injury treatment.In summary,we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury.Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

关键词： meniscus injuries cartilage

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胚胎干细胞体外减数分裂获得功能配子

科学新闻 2017年第4期 63-63页

作者： Quan Zhou Mei Wang Yan Yuan Xuepeng Wang Rui Fu Haifeng Wan Mingming Xie Mingxi Liu Xuejiang Guo Ying Zheng guihai feng Qinghua Shi 赵小阳沙家豪周琪南方医科大学南京医科大学生殖医学国家重点实验室中科院中科院动物研究所中科院大学

文章简介随着不孕不育症的全球性高发,通过体外培养的方式获得功能配子被认为是解决不孕不育症生殖细胞缺乏问题最为有效的途径,但过往的研究表明真实的再现减数分裂过程是体外获得功能配子难以逾越的障碍。本研究首先将小鼠胚胎干细胞... 详细信息

文章简介随着不孕不育症的全球性高发,通过体外培养的方式获得功能配子被认为是解决不孕不育症生殖细胞缺乏问题最为有效的途径,但过往的研究表明真实的再现减数分裂过程是体外获得功能配子难以逾越的障碍。本研究首先将小鼠胚胎干细胞分化成原始生殖细胞样细胞,与不育症(KitW/KitW-V)小鼠睾丸细胞共培养及多种细

关键词：减数分裂干细胞成熟分裂配子配偶子配子体不孕不育症原始生殖细胞功能

Ti-28Ni钎料真空钎焊TZM合金接头界面组织与力学性能

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稀有金属材料与工程 2018年第3期47卷 927-931页

作者：田骁赵洪运宋晓国韩桂海冯吉才哈尔滨工业大学先进焊接与连接国家重点实验室黑龙江哈尔滨150001 哈尔滨工业大学(威海)山东省特种焊接技术重点实验室山东威海264209 山东省科学院海洋仪器仪表研究所山东青岛266001

在钎焊温度为1040℃时,采用Ti-28Ni(质量分数,%)钎料实现了TZM合金的真空钎焊连接。采用SEM、EDS等方法分析了接头界面的微观组织结构,并研究了保温时间对TZM合金接头界面结构和性能的影响规律。结果表明,接头的典型界面组织结构为:TZM/... 详细信息

在钎焊温度为1040℃时,采用Ti-28Ni(质量分数,%)钎料实现了TZM合金的真空钎焊连接。采用SEM、EDS等方法分析了接头界面的微观组织结构,并研究了保温时间对TZM合金接头界面结构和性能的影响规律。结果表明,接头的典型界面组织结构为:TZM/Ti_(ss)/δ-Ti2Ni/Ti_(ss)/TZM;随保温时间的延长,焊缝宽度逐渐变小,其中连续的Ti_(ss)层厚度基本无变化,中间的δ-Ti_2Ni层厚度有所降低;同时,TZM母材向焊缝中的溶解量增加。保温时间较短时,焊缝中残留有未溶解的TZM块,延长保温时间使母材溶解更充分。当保温时间为10 min时,接头平均抗剪强度最高为92.6 MPa,断裂发生于δ-Ti_2Ni层,为脆性沿晶断裂。

关键词： TZM合金真空钎焊界面组织力学性能

职工血脂水平及血脂异常患病率调查分析及对策

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中国社区医师 2014年第21期 116-117+119页

作者：徐宁田利源冯桂海高镇北北京市中国人民银行营业管理部医务室北京市崇文光明医院北京市中科院遗传与发育生物研究所

目的:调查北京某单位人群的血脂水平、分布特征及血脂异常患病率,并探讨血脂水平与体重指数(BMI)的关系,为有针对性地开展健康教育及干预提供依据。方法:将单位职工按性别、年龄分组,应用统计学方法分析各个组的体重指数(BMI)、血脂水... 详细信息

目的:调查北京某单位人群的血脂水平、分布特征及血脂异常患病率,并探讨血脂水平与体重指数(BMI)的关系,为有针对性地开展健康教育及干预提供依据。方法:将单位职工按性别、年龄分组,应用统计学方法分析各个组的体重指数(BMI)、血脂水平及血脂异常患病率。用Pearson相关性分析探讨血脂水平与体重指数的关系。结果:男性30岁组较20岁组BMI、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)的增长最为显著,而女性40岁组较30岁组的BMI、TC、TG、LDL-C增长显著。血脂异常在男性以高甘油三酯血症为主,而女性则以高胆固醇血症为主。BMI与女性血脂水平特别是甘油三酯水平更为相关。结论:对青年男性及更年期女性需要及早采取措施控制血脂水平,控制体重对于降低血脂水平是必要的。

关键词：血脂水平高脂血症超重健康教育