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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

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 Research School of Life Sciences and Technology Tongji University Frontier Science Center for Stem cell Research Tongji University Shanghai Tenth People's Hospital School of Medicine Tongji University Key laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji Hospital Tongji University Shanghai Institute of Stem cell Research and Clinical Translation

The TET family is well known for active DNA demethylation and plays important roles in regulating transcription, the epigenome and development. Nevertheless, 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 enough. To 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 lethality. Notably, 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 methylation. Intriguingly, 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 mESCs. Notably, there were common regulatory regions between Tet1 and Tet3 in pluripotency regulation. In summary, our study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.

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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

维普期刊数据库

OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem cell Self-Renewal and Apoptosis through cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

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Research 2024年第1期2023卷 455-469页

作者： Yinghong Cui Wei Chen Li Du Zuping He The Key laboratory of Model Animals and Stem cell Biology in Hunan Province The Research Center of Reproduction and Translational Medicine of Hunan ProvinceHunan Normal University School of MedicineChangsha 410013HunanChina

Spermatogonial stem cells(SSCs)have important applications in both reproduction and regenerative ***,specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain ***,we have demonstrated for the first time that OIP5(Opa interacting protein 5)controlled the self-renewal and apoptosis of human *** sequencing identified that NCK2 was a target for OIP5 in human SSCs,and interestingly,OIP5 could interact with NCK2 as shown by Co-IP(co-immunoprecipitation),IP-MS(mass spectrometry),and GST pulldown ***2 silencing decreased human SSC proliferation and DNA synthesis but enhanced their ***,NCK2 knockdown reversed the influence of OIP5 overexpression on human ***,OIP5 inhibition decreased the numbers of human SSCs at S and G2/M phases,while the levels of numerous cell cycle proteins,including cyclins A2,B1,D1,E1 and H,especially cyclin D1,were remarkably ***,whole-exome sequencing of 777 patients with nonobstructive azoospermia(NOA)revealed 54 singlenucleotide polymorphism mutations of the OIP5 gene(6.95%),while the level of OIP5 protein was obviously lower in testes of NOA patients compared to fertile ***,these results implicate that OIP5 interacts with NCK2 to modulate human SSC self-renewal and apoptosis via cell cyclins and cell cycle progression and that its mutation and/or lower expression is correlated with *** such,this study offers novel insights into molecular mechanisms underlying the fate determinations of human SSCs and the pathogenesis of NOA,and it provides new targets for treating male infertility.

关键词： OIP5 Apoptosis reversed

Notoginsenoside Ft1 inhibits colorectal cancer growth by increasing CD8^(+)T cell proportion in tumor-bearing mice through the USP9X signaling pathway

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Chinese Journal of Natural Medicines 2024年第4期22卷 329-340页

作者： FENG Yutao LI Yuan MA Fen WU Enjiang CHENG Zewei ZHOU Shiling WANG Zhengtao YANG Li SUN Xun ZHANG Jiwei Shanghai Key laboratory of Compound Chinese Medicines The MOE Key Laboratory for Standardization of Chinese MedicinesInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Gastrointestinal surgery Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

The management of colorectal cancer(CRC)poses a significant challenge,necessitating the development of innovative and effective *** research has shown that notoginsenoside Ft1(Ng-Ft1),a small molecule,markedly inhibits subcutaneous tumor formation in CRC and enhances the proportion of CD8^(+)T cells in tumor-bearing mice,thus restraining tumor *** into the mechanism revealed that Ng-Ft1 selectively targets the deubiquitination enzyme USP9X,undermining its role in shieldingβ-*** leads to a reduction in the expression of downstream effectors in the Wnt signaling *** findings indicate that Ng-Ft1 could be a promising small-molecule treatment for CRC,working by blocking tumor progression via the Wnt signaling pathway and augmenting CD8^(+)T cell prevalence within the tumor environment.

关键词： Notoginsenoside Ft1 Colorectal cancer CD8^(+)T cell Ubiquitin-specific peptidase 9 X-linked β-Catenin Wnt

Diverse functions of sox9 in liver development and homeostasis and hepatobiliary diseases

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Genes & Diseases 2024年第4期11卷 170-187页

作者： Taiyu Shang Tianyi Jiang Xiaowen Cui Yufei Pan Xiaofan Feng Liwei Dong Hongyang Wang School of Life Sciences Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China National Center for Liver Cancer The Naval Medical UniversityShanghai 201805China International Cooperation laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteThe Second Military Medical UniversityShanghai 200438China laboratory of signaling Regulation and Targeting Therapy of Liver Cancer Second Military Medical University&Ministryof EducationShanghai 200438China

The liver is the central organ for digestion and detoxification and has unique metabolic and regenerative *** hepatobiliary system originates from the foregut endoderm,in which cells undergo multiple events of cell proliferation,migration,and differentiation to form the liver parenchyma and ductal system under the hierarchical regulation of transcription *** on liver development and diseases have revealed that SRY-related high-mobility group box 9(SOx9)plays an important role in liver embryogenesis and the progression of hepatobiliary ***9 is not only a master regulator of cell fate determination and tissue morphogenesis,but also regulates various biological features of cancer,including cancer stemness,invasion,and drug resistance,making Sox9 a potential biomarker for tumor prognosis and *** review systematically summarizes the latest findings of sox9 in hepatobiliary development,homeostasis,and *** also highlight the value of sox9 as a novel biomarker and potential target for the clinical treatment of major liverdiseases.

关键词： Biliary system Cancer Homeostasis Liver diseases SOX9

RACK1A promotes hypocotyl elongation by scaffolding light signaling components in Arabidopsis

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Journal of Integrative Plant Biology 2024年第5期66卷 956-972页

作者： Yajuan Fu Wei Zhu Yeling Zhou Yujing Su Zhiyong Li Dayan Zhang Dong Zhang Jinyu Shen Jiansheng Liang Key laboratory of Molecular Design for Plant cell Factory of Guangdong Higher Education Institutes Department of BiologySchool of Life SciencesInstitute of Plant and Food SciencesSouthern University of Science and TechnologyShenzhen 518055China

Plants deploy versatile scaffold proteins to intricately modulate complex cell *** these,RACK1A(Receptors for Activated C Kinase 1A)stands out as a multifaceted scaffold protein functioning as a central integrative hub for diverse signaling ***,the precise mechanisms by which RACK1A orchestrates signal transduction to optimize seedling development remain largely ***,we demonstrate that RACK1A facilitates hypocotyl elongation by functioning as a flexible platform that connects multiple key components of light signaling ***1A interacts with PHYTOCHROME INTERACTING FACTOR(PIF)3,enhances PIF3 binding to the promoter of BBX11 and down-regulates its ***,RACK1A associates with ELONGATED HYPOCOTYL 5(HY5)to repress HY5 biochemical activity toward target genes,ultimately contributing to hypocotyl *** darkness,RACK1A is targeted by CONSTITUTIVELY PHOTOMORPHOGENIC(COP)1 upon phosphorylation and subjected to COP1-mediated degradation via the 26 S proteasome *** findings provide new insights into how plants utilize scaffold proteins to regulate hypocotyl elongation,ensuring proper skoto-and photo-morphogenic development.

关键词： Arabidopsis hypocotyl development light signaling components RACK1 scaffoldprotein

维普期刊数据库

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

Dear-DIA^(XMBD): Deep Autoencoder Enables Deconvolution of Data-Independent Acquisition Proteomics

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Research 2024年第1期6卷 707-720页

作者： Qingzu He Chuan-Qi Zhong Xiang Li Huan Guo Yiming Li Mingxuan Gao Rongshan Yu Xianming Liu Fangfei Zhang Donghui Guo Fangfu Ye Tiannan Guo Jianwei Shuai Jiahuai Han Department of Physics and Fujian Provincial Key Laboratory for Soft Functional Materials ResearchXiamen UniversityXiamen 361005China Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)and Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang 325001China School of Life Sciences Xiamen UniversityXiamen 361102China State Key laboratory of cellular Stress Biology Innovation Center for Cell Signaling NetworkXiamen 361102China Department of Computer Science Xiamen UniversityXiamen 361005China National Institute for Data Science in Health and Medicine School of MedicineXiamen UniversityXiamen 361102China Bruker(Beijing)Scientific Technology Co.Ltd. BeijingChina Westlake laboratory of Life Sciences and Biomedicine Key Laboratory of Structural Biology of Zhejiang ProvinceSchool of Life SciencesWestlake University18 Shilongshan RoadHangzhou 310024China Institute of Basic Medical Sciences Westlake Institute for Advanced Study18 Shilongshan RoadHangzhou 310024China Westlake Omics Ltd. Yunmeng Road 1HangzhouChina Department of Electronic Engineering Xiamen UniversityXiamen 361005China

Data-independent acquisition(DIA)technology for protein identification from mass spectrometry and related algorithms is developing *** spectrum-centric analysis of DIA data without the use of spectra library from data-dependent acquisition data represents a promising *** this paper,we proposed an untargeted analysis method,Dear-DIA^(XMBD),for direct analysis of DIA ***-DIA^(XMBD) first integrates the deep variational autoencoder and triplet loss to learn the representations of the extracted fragment ion chromatograms,then uses the k-means clustering algorithm to aggregate fragments with similar representations into the same classes,and finally establishes the inverted index tables to determine the precursors of fragment clusters between precursors and peptides and between fragments and *** show that Dear-DIA^(XMBD) performs superiorly with the highly complicated DIA data of different species obtained by different instrument platforms.

关键词： Deep Auto Independent

Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression

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Frontiers of Medicine 2024年第3期18卷 430-445页

作者： Yue Ma Hongwei Lv Fuxue Xing Wei Xiang Zixin Wu Qiyu Feng Hongyang Wang Wen Yang Cancer Research Center First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei230027China National Center for Liver Cancer Naval Medical University(Second Military Medical University)Shanghai201805China International Co-operation laboratory on Signal Transduction Eastern Hepatobiliary Surgery HospitalNaval Medical University(Second Military Medical University)Shanghai200438China Shanghai Key laboratory of Hepato-biliary Tumor Biology Shanghai200438China Key laboratory of signaling Regulation and Targeting Therapy of Liver Cancer Ministry of EducationShanghai200438China

Crosstalk between cancer cells and the immune microenvironment is determinant for liver cancer progression.A tumor subpopulation called liver cancer stem cells(CSCs)significantly accounts for the initiation,metastasis,therapeutic resistance,and recurrence of liver *** evidence demonstrates that the interaction between liver CSCs and immune cells plays a crucial role in shaping an immunosuppressive microenvironment and determining immunotherapy *** review sheds light on the bidirectional crosstalk between liver CSCs and immune cells for liver cancer progression,as well as the underlying molecular mechanisms after presenting an overview of liver CSCs characteristic and their ***,we discuss the potential application of liver CSCs-targeted immunotherapy for liver cancer treatment.

关键词： liver cancer cancer stem cell immune cell immunotherapy