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Transcriptome Dynamics and Cell Dialogs Between Oocytes and Granulosa Cells in Mouse Follicle Development

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 93-106页

作者： Wenju Liu Chuan Chen Yawei gao Xinyu Cui Yuhan Zhang Liang Gu Yuanlin He Jing Li shaorong gao Rui gao Cizhong Jiang Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell Research Tongji UniversityShanghai 200092China Department of Epidemiology and Biostatistics Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjing 210029China

The development and maturation of follicles is a sophisticated and multistage *** dynamic gene expression of oocytes and their surrounding somatic cells and the dialogs between these cells are critical to this *** this study,we accurately classified the oocyte and follicle development into nine stages and profiled the gene expression of mouse oocytes and their surrounding granulosa cells and cumulus *** clustering of the transcriptomes showed the trajectories of two distinct development courses of oocytes and their surrounding somatic *** expression changes precipitously increased at Type 4 stage and drastically dropped afterward within both oocytes and granulosa ***,the number of differentially expressed genes between oocytes and granulosa cells dramatically increased at Type 4 stage,most of which persistently passed on to the later ***,cell communications within and between oocytes and granulosa cells became active from Type 4 stage *** dialogs connected oocytes and granulosa cells in both unidirectional and bidirectional ***2/3,TGFBR2/3,INHBA/B,and ACVR1/1B/2B of TGF-βsignaling pathway functioned in the follicle *** signaling pathway regulated the development of granulosa ***,many maternally DNA methylation-or H3K27me3-imprinted genes remained active in granulosa cells but silent in oocytes during ***,Type 4 stage is the key turning point when significant transcription changes diverge the fate of oocytes and granulosa cells,and the cell dialogs become active to assure follicle *** findings shed new insights on the transcriptome dynamics and cell dialogs facilitating the development and maturation of oocytes and follicles.

关键词： Folliculogenesis Oocyte Granulosa cell Transcriptome Cell dialog

Pivotal role for long noncoding RNAs in zygotic genome activation in mice

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Science China(Life Sciences) 2024年第5期67卷 958-969页

作者： Kang Chen Wenju Liu Jiang Zhu Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang shaorong gao Lan Kang Institute for Regenerative Medicine Shanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell Research Tongji UniversityShanghai 200092China Clinical and Translation Research Center of Shanghai First Maternity&Infant Hospital School of Life Sciences and TechnologyTongji UniversityShanghai 200092China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Vertebrate life begins with fertilization,and then the zygote genome is activated after transient silencing,a process termed zygotic genome activation(ZGA).Despite its fundamental role in totipotency and the initiation of life,the precise mechanism underlying ZGA initiation remains *** existence of minor ZGA implies the possible critical role of noncoding RNAs in the initiation of ***,we delineate the expression profile of long noncoding RNAs(lncRNAs)in early mouse embryonic development and elucidate their critical role in minor *** with protein-coding genes(PCGs),lncRNAs exhibit a stronger correlation with minor *** H3K9me3 profiles can be observed between lncRNA genes and PCGs,and the enrichment of H3K9me3 before ZGA might explain the suspended expression of major ZGA-related PCGs despite possessing PolII ***,we identified the presence of PolII-enriched MuERV-L around the transcriptional start site of minor ZGA-related lncRNAs,and these repeats are responsible for the activation of minor ZGA-related lncRNAs and subsequent embryo *** study suggests that MuERV-L mediates minor ZGA lncRNA activation as a critical driver between epigenetic reprogramming triggered by fertilization and the embryo developmental program,thus providing clues for understanding the regulatory mechanism of totipotency and establishing bona fide totipotent stem cells.

关键词： ZGA lncRNA MuERV-L

Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

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National Science Review 2024年第2期11卷 124-134页

作者： Jingyu Li Weibo Hou Qi Zhao Wei Han Hongdi Cui Songling Xiao Ling Zhu Jiadan Qu Xiaoyu Liu Weitao Cong Jingling Shen Yuzheng Zhao shaorong gao Guoning Huang Qingran Kong Chongqing Key Laboratory of Human Embryo Engineering Center for Reproductive Medicine Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical University Oujiang Laboratory Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life Sciences Wenzhou Medical University Frontier Science Center for Stem Cell Research School of Life Sciences and Technology Tongji University School of Pharmaceutical Science Wenzhou Medical University Institute of Life Sciences College of Life and Environmental Sciences Wenzhou University Optogenetics&Synthetic Biology Interdisciplinary Research Center State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation(ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-Co A and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

关键词： mammalian preimplantation development lactate epigenetic remodeling histone lactylation zygotic genome activation

Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics

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Protein & Cell 2024年第7期15卷 530-546页

作者： Tao Chen Yiliang Xu Xiaocui Xu Jianzhang Wang Zhiruo Qiu Yayuan Yu Xiaohong Jiang Wanqi Shao Dandan Bai Mingzhu Wang Shuyan Mei Tao Cheng Li Wu shaorong gao Xuan Che Department of Obstetrics and Gynecology Affiliated Women and Children Hospital of Jiaxing UniversityJiaxing 314000China Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Key Laboratory of Animal Bioengineering and Disease Prevention of Shandong Province College of Animal Science and TechnologyShandong Agricultural UniversityTaian 271018China Women’s Hospital School of MedicineZhejiang UniversityHangzhou 310013China Postgraduate training base Alliance of Wenzhou Medical University Wenzhou Medical UniversityWenzhou 325035China Jiaxing University Master Degree Cultivation Base Zhejiang Chinese Medical UniversityHangzhou 310053China Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyClinical and Translational Research CenterShanghai First Maternity and Infant HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

Adenomyosis is a poorly understood gynecological disorder lacking effective *** persists regarding“invagination”and“metaplasia”*** endometrial-myometrial junction(EMJ)connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis,but its in-depth study is just *** single-cell RNA sequencing and spatial profiling,we mapped transcriptional alterations across eutopic endometrium,lesions,and *** lesions,we identified unique epithelial(LGR5+)and invasive stromal(PKIB+)subpopulations,along with WFDC1+progenitor cells,supporting a complex interplay between“invagination”and“metaplasia”theories of ***,we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin ***-cell communication differed markedly between ectopic and eutopic endometrium,with aberrant signaling in lesions involving pleiotrophin,TWEAK,and WNT *** study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified,dysfunctional signaling,and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.

关键词： adenomyosis single-cell RNA sequencing spatial transcriptomics endometrial-myometrial junction progenitor cells

Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects

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Science China(Life Sciences) 2024年第10期67卷 2132-2148页

作者： Mengting Wang Liping Wang Yanxin Huang Zhibin Qiao Shanru Yi Weina Zhang Jing Wang Guang Yang Xinyu Cui Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang shaorong gao Jiayu Chen Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Shanghai Tenth People’s Hospital School of MedicineTongji UniversityShanghai 200072China Frontier Science Center for Stem Cell Research Tongji UniversityShanghai 200092China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China Shanghai Institute of Stem Cell Research and Clinical Translation Shanghai 200120China

The TET family is well known for active DNA demethylation and plays important roles in regulating transcription,the epigenome and ***,previous studies using knockdown(KD)or knockout(KO)models to investigate the function of TET have faced challenges in distinguishing its enzymatic and nonenzymatic roles,as well as compensatory effects among TET family members,which has made the understanding of the enzymatic role of TET not accurate *** solve this problem,we successfully generated mice catalytically inactive for specific Tet members(Tetm/m).We observed that,compared with the reported KO mice,mutant mice exhibited distinct developmental defects,including growth retardation,sex imbalance,infertility,and perinatal ***,Tetm/mmouse embryonic stem cells(mESCs)were successfully established but entered an impaired developmental program,demonstrating extended pluripotency and defects in ectodermal differentiation caused by abnormal DNA ***,Tet3,traditionally considered less critical for m ESCs due to its lower expression level,had a significant impact on the global hydroxymethylation,gene expression,and differentiation potential of ***,there were common regulatory regions between Tet1 and Tet3 in pluripotency *** summary,our study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.

关键词： Tet hydroxymethylase activity mESCs DNA demethylation 5hmC

Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy

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Protein & Cell 2024年第6期15卷 460-473页

作者： Chenxiang Xi Zihui Yan Dandan Bai Yalin Zhang Beiying Wang Xiaoxiao Han Li Wu Xiaohui Shi Zhiyi Hu Ming Tang Zhongqu Su Yingdong Liu Binya Liu Jiqing Yin Hong Wang Xiaocui Li Yanping Zhang shaorong gao Wenqiang Liu Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalShanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Jiaxing Maternity and Child Health Care Hospital Jiaxing 314050China

The current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)remains a threat to pregnant ***,the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly ***,we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early *** to control placentas,SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks ***,subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal ***,the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second *** study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.

关键词： fetal alterations pregnancy

Effect of SARS-CoV-2 infection in early pregnancy on placental development

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Science China(Life Sciences) 2024年第3期67卷 622-625页

作者： Shanru Yi Liping Wang Mengting Wang Wei Hong Ben Xu Xiaoying He Mengtian Yang Zhiping Wu Beiying Wang Guang Yang Shijun Shen Xinyu Cui Ruixue Wang Kai Wang Hong Wang Xiaocui Li shaorong gao Cizhong Jiang Jiayu Chen Clinical and Translation Research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China Frontier Science Center for Stem cell Research Tongji UniversityShanghai 200092China Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai 201204China

Dear Editor,Since the COVID-19 pandemic, the potential risks associated with maternal SARS-CoV-2 infection and its effect on fetal development have been a subject of considerable public concern. Previous studies have ... 详细信息

关键词： pregnancy fetal Effect

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人类早期胚胎发育过程中组蛋白修饰的调控

中国科学：生命科学 2024年第1期54卷 84-93页

作者：徐睿敏李翀刘晓雨高绍荣同济大学生命科学与技术学院上海市信号与疾病研究重点实验室上海市东方医院再生医学研究所上海200120 同济大学生命科学与技术学院上海市第一妇婴保健院转化医学中心上海市母胎医学与妇科肿瘤研究所上海市母胎医学重点实验室上海200092 同济大学教育部细胞干性与命运编辑前沿科学中心上海200092

哺乳动物的生命起源于两个终末分化的生殖细胞的结合(受精),随即父母源的染色质发生剧烈且精确的表观遗传重编程,并形成具有全能性的胚胎.研究早期胚胎发育是理解物种延续和进化的重要途径,也为女性生殖健康和再生医学提供了重要理论依... 详细信息

哺乳动物的生命起源于两个终末分化的生殖细胞的结合(受精),随即父母源的染色质发生剧烈且精确的表观遗传重编程,并形成具有全能性的胚胎.研究早期胚胎发育是理解物种延续和进化的重要途径,也为女性生殖健康和再生医学提供了重要理论依据.然而,由于高等哺乳动物早期胚胎的稀缺性和伦理问题,以及高通量表观修饰检测技术的限制,目前对于人类早期胚胎中的表观遗传重编程的研究还不全面.利用最近建立的超低起始量的高通量测序技术,我国科学家首次揭示了多种组蛋白修饰在人类早期胚胎发育过程中的动态变化和调控机制.本文主要对这几项最新的研究进展进行了总结,并对人类和小鼠早期胚胎中的组蛋白修饰重编程的保守性和物种特异性进行了讨论.

关键词：人类早期胚胎表观遗传重编程组蛋白修饰合子基因组激活逆转座子

Cloning non-HUMAN primates by somatic cell nuclear transfer

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Science China(Life Sciences) 2018年第3期61卷 361-362页

作者： shaorong gao Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital School of Life Sciences and Technology Tongji University

The recent breakthrough in successful producing cloned non- human primates by somatic cell nuclear transfer （SCNT） has attracted great attention both scientifically and publically （Liu et al., 2018）. Two macaque monkeys, named ＂Zhongzhong＂ and ＂Huahua＂, were cloned from fetal fi- broblast cells by Chinese scientists using the technique that produced the first cloned mammal ＂Dolly＂ 21 years ago （Wilmut et al., 1997）. The first cloned sheep has re- volutionized our thinking that the mammalian somatic cells can be reprogrammed into totipotent embryos by SCNT, although the efficiency is extremely low. Actually, in the same year when ＂Dolly＂ was reported, a paper published in Biology of Reproduction also attracted broad attention in which two rhesus monkeys were produced from blastomeres isolated from 4-cell stage embryos using the same technique （Meng et al., 1997）. However, it remains very challenging if the somatic cells from monkeys can be reprogrammed into totipotent embryos, although many laboratories all over the world have tried very hard in the past 20 years. Indeed, the successful cloning of monkeys today is attributed to both the technical improvement and the progress obtained in me- chanistic studies in reprogramming. Two major techniques are involved in SCNT. The first is called enucleation through which the spindle-chromosome complex （SCC） of an oocyte at metaphase II （MII） stage is removed by an enucleation pipette. The enucleation process is relatively easy for mouse oocytes since the SCC can be visualized under light micro- scope, but the SCC of oocytes from large animals including

关键词：原子转移克隆房间技术改进人类卵母细胞哺乳动物 SCC