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“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Juan Su~a,Pu You~a,Wen-Lin Li~a,Xin-Rong Tao~a,Hai-Ying Zhu~a,Yu-cheng Yao~(a,b),Hong-Yu Yu~c,Qing-Wang Han~a,Bing Yu~a, Fang-Xia Liu~a,Jun Xu~d,Joseph T.Y.Lau~e,and Yi-Ping Hu~a a.department of cell biology,Second Military Medical University,Xiangyin Rd.800,Shanghai 200433,P.R.china b.Division of cardiology,University of california,Los Angeles,cA 90095,united states c.department of Pathology,changzheng hospital,Fcngyang Rd.415,Shanghai 200003,P.R.china d department of Pathology,No.105 Hospital of PLA,Hefei 230031,P.R.china c.department of molecular and cellular biology,roswell park cancer institute,buffalo,new york,ny 10021,united states

During early stage of embryonic development,the liver bud,arising from the foregut endoderm, is the beginning for the formation of future liver three-dimensional *** the gene expression profiles associated with this developmental stage have been well explored,the detailed cellular events are not as ***-mesenchymal transition(EMT) was thought to be essential for cell migration in the early vertebrate embryo but seldom demonstrated in human liver *** this study,we tried to identify the cell populations with both stem cell and EMT features in the human liver *** in situ studies show that the phenotype of EMT occurs at initiation of human liver development,accompanied by up-regulation of EMT associated genes.A human liver bud derived stem cell line(hLBSc) was established, which expressed not only genes specific to both mesenchymal cells and hepatic cells,but also Octamer-binding protein 4(OcT4) and *** in appropriate media,hLBSc differentiated into hepatocytes,adipocytes,osteoblast-like cells and neuron-like cells in *** transplanted into severe combined immunodeficiency mice pre-treated by carbon tetrachloride,hLBSc engrafted into the liver parenchyma and *** data suggest that mere are cell populations with stem cell and EMT-like properties in the human liver bud,which may play an important role in the beginning of the spatial structure construction of the liver.

关键词： epithelial-mesenchymal transition liver bud liver development multipotent stem cells fetal liver

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RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts

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cellular & molecular Immunology 2023年第1期20卷 94-109页

作者： Seyeon Bae Kibyeong Kim Keunsoo Kang Haemin Kim Minjoon Lee Brian Oh Kaichi Kaneko Sungkook Ma Jae Hoon choi Hojoong Kwak Eun Young Lee Sung Ho park Kyung-Hyun park-Min Arthritis and Tissue Degeneration Program David Z.Rosensweig Genomics Research CenterHospital for Special SurgeryNew YorkNY10021USA department of Medicine Weill Cornell Medical CollegeNew YorkNY10065USA department of Biological Science Ulsan National Institute of Science&Technology(UNIST)Ulsan44919Republic of Korea department of Life Science College of Natural SciencesResearch Institute for Natural SciencesHanyang UniversitySeoulKorea department of Microbiology Dankook UniversityCheonan3116Republic of Korea department of molecular biology and Genetics Cornell UniversityIthacaUSA Division of Rheumatology Department of Internal MedicineSeoul National University College of MedicineSeoulKorea BcMB Allied Program Weill Cornell Graduate School of Medical SciencesNew YorkNY10021USA

Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from chIP-seq, ATAc-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, cD4+ T cells, and cD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to t

关键词： Osteoclasts super-enhancers enhancer RNAs Rheumatoid arthritis

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MicroRNAs in pancreatic ductal adenocarcinoma

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World Journal of Gastroenterology 2011年第7期17卷 817-827页

作者： Jong Y park James Helm Domenico coppola Donghwa Kim Mokenge Malafa Seung Joon Kim Division of cancer Prevention and control Moffitt Cancer Center FL 33612 United States Gastrointestinal Tumor Program Moffitt Cancer Center FL 33612 United States department of Anatomic Pathology Moffitt Cancer Center FL 33612 United States department of molecular Oncology MoffittCancer Center FL 33612 United States department of Internal Medicine Collegeof Medicine the Catholic University of Korea Seoul 137-040South Korea

Ductal adenocarcinoma of the pancreas is a lethal cancer for which the only chance of long-term survival belongs to the patient with localized disease in whom a potentially curative resection can be done. Therefore, biomarkers for early detection and new therapeutic strategies are urgently needed. miRNAs are a recently discovered class of small endogenous non-coding RNAs of about 22 nucleotides that have gained attention for their role in downregulation of mRNA expression at the post-transcriptional level. miRNAs regulate proteins involved in critical cellular processes such as differentiation, proliferation, and apoptosis. Evidence suggests that deregulated miRNA expression is involved in carcinogenesis at many sites, including the pancreas. Aberrant expression of miRNAs may upregulate the expression of oncogenes or downregulate the expression of tumor suppressor genes, as well as play a role in other mechanisms of carcinogenesis. The purpose of this review is to summarize our knowledge of deregulated miRNA expression in pancreatic cancer and discuss the implication for potential translation of this knowledge into clinical practice.

关键词： MicroRNAs Pancreatic cancer

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Emerging roles of circular RNAs in retinal diseases

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Neural Regeneration Research 2022年第9期17卷 1875-1880页

作者： Aneliya Hanineva Karen Sophia park Joshua J.Wang Margaret M.DeAngelis Michael H.Farkas Sarah X.Zhang department of Ophthalmology and Ross Eye institute Jacobs School of Medicine and Biomedical SciencesUniversity at BuffaloState University of New YorkBuffaloNYUSA Research Service Veterans Administration Western New York Healthcare SystemBuffaloNYUSA department of Biochemistry Jacobs School of Medicine and Biomedical SciencesUniversity at BuffaloState University of New YorkBuffaloNYUSA

Retinal disorders are a group of ocular diseases whose onset is associated with a number of aberrant molecular and cellular processes or physical damages that affect retinal structure and function resulting in neural and vascular degeneration in the *** research has primarily focused on delaying retinal disease with minimal success in preventing or reversing neuronal *** this review,we explore a relatively new field of research involving circular RNAs,whose potential roles as biomarkers and mediators of retinal disease pathogenesis have only just *** knowledge of circular RNAs function is limited given its novelty,current evidence has highlighted their roles as modulators of microRNAs,regulators of gene transcription,and biomarkers of disease development and ***,we summarize how circular RNAs may be implicated in the pathogenesis of common retinal diseases including diabetic retinopathy,glaucoma,proliferative vitreoretinopathy,and age-related macular ***,we explore the potential of circular RNAs as novel biomarkers and therapeutic targets for the diagnosis and treatment of retinal diseases.

关键词： age-related macular degeneration circular RNA diabetic retinopathy glaucoma microRNA proliferative vitreoretinopathy retina

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Human mesenchymal stem cells derived from umbilical cord and bone marrow exert immunomodulatory effects in different mechanisms

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World Journal of Stem cells 2020年第9期12卷 1032-1049页

作者： Yunejin Song Jung-Yeon Lim Taekyu Lim Keon-Il Im Nayoun Kim Young-Sun Nam Young-Woo Jeon Jong chul Shin Hyun Sun Ko In Yang park Seok-Goo cho institute for Translational Research and molecular Imaging College of MedicineThe Catholic University of KoreaSeoul 06591South Korea Laboratory of Immune Regulation Convergent Research Consortium for Immunologic DiseaseCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea department of Biomedicine and Health Sciences College of MedicineThe Catholic University of KoreaSeoul 06591South Korea Precision Immunology institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Division of Hematology Oncology Department of Internal MedicineVeterans Health Service Medical CenterSeoul 05368South Korea department of Hematology Catholic Blood and Marrow Transplantation CenterSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea department of Obstetrics and Gynecology CHA Bundang Medical CenterCHA UniversitySeongnam 13496South Korea department of Obstetrics and Gynecology College of MedicineThe Catholic University of KoreaSeoul 06591South Korea Division of Hematology Department of Internal MedicineCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea

BAcKGROUND Mesenchymal stem cells(MScs)are an attractive tool to treat graft-versus-host disease because of their unique immunoregulatory *** human bone marrow-derived MScs(BM-MScs)were the most widely used MScs in cell therapy until recently,MScs derived from human umbilical cords(Uc-MScs)have gained popularity as cell therapy material for their ethical and noninvasive *** To investigate the difference in mechanisms of the immunosuppressive effects of Uc-MScs and *** To analyze soluble factors expressed by MScs,such as indolamine 2,3-dioxygenase,cyclooxygenase-2,prostaglandin E2 and interleukin(IL)-6,inflammatory environments in vitro were reconstituted with combinations of interferon-gamma(IFN-γ),tumor necrosis factor alpha and IL-1βor with IFN-γ*** T cells were cocultured with MScs treated with indomethacin and/or *** assess the ability of MScs to inhibit T helper 17 cells and induce regulatory T cells,induced T helper 17 cells were cocultured with MScs treated with indomethacin or *** graft-versus-host disease was induced in NOG mice(NOD/Shi-scid/IL-2Rγnull)and Uc-MScs or BM-MScs were treated as cell *** Our data demonstrated that BM-MScs and Uc-MScs shared similar phenotypic characteristics and immunomodulation ***-MScs expressed more indolamine 2,3-dioxygenase after cytokine stimulation with different combinations of IFN-γ,tumor necrosis factor alpha-αand IL-1βor IFN-γ***-MScs expressed more prostaglandin E2,IL-6,programmed death-ligand 1 and 2 in the in vitro inflammatory ***-2 and IL-10 were key factors in the immunomodulatory mechanisms of both *** addition,Uc-MScs inhibited more T helper 17 cells and induced more regulatory T cells than ***-MScs and BM-MScs exhibited similar effects on attenuating graft-versus-host *** Uc-MScs and BM-MScs exert similar immunosuppressive effects with different mechanisms

关键词： Mesenchymal stem cells Graft-versus-host disease Umbilical cord cell therapy Xenogeneic mouse model Immunomodulation

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Multidisciplinary perspective of hepatocellular carcinoma: A Pacific Northwest experience

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World Journal of Hepatology 2015年第11期7卷 1460-1483页

作者： Matthew M Yeh Raymond S Yeung Smith Apisarnthanarax Renuka Bhattacharya carlos cuevas William P Harris Tony Lim Kiat Hon Siddharth A Padia James O park Kevin M Riggle Sayed S Daoud department of Pathology University of Washington School of Medicine department of Medicine University of Washington School of Medicine Northwest Liver Research Program Depart-ment of Surgery University of Washington School of Medicine department of Radiation Oncology University of Washington School of Medicine department of Radiology University of Washington School of Medicine Seattle department of Pathology Singapore General Hospital department of Pharmaceutical Sciences Washington State University Health Sciences

Hepatocellular carcinoma(Hcc) is the most rapidly increasing type of cancer in the united states. Hcc is a highly malignant cancer, accounting for at least 14000 deaths in the united states annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with Hcc are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. clearly there is need of a multidisciplinary approach for the management of Hcc. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would:(1) greatly facilitate the identification of patients at risk;(2) prompt efforts to decrease risk factors; and(3) improve surveillance and early diagnosis through diagnostic imaging modalities. Possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of Hcc,this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of Hcc that include: molecular hepatocarcinogenesis, noninvasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics.

关键词： Genetic alterations Epigenetic alterations Diagnostic pathology Diagnostic imaging Surgicalmodality Liver transplantation Locoregional therapy Sorafenib Hepatocellular carcinoma Liver resection

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Lineage relationship of cD8^＋ T cell subsets is revealed by progressive changes in the epigenetic landscape

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cellular & molecular Immunology 2016年第4期13卷 502-513页

作者： Joseph G. crompton Manikandan Narayanan Suresh cuddapah Rahul Roychoudhuri Yun Ji Wenjing Yang Shashank J. Patel Madhusudhanan Sukumar Douglas c. Palmer Weiqun Peng Ena Wang Francesco M. Marincola christopher A. Klebanoff Keji Zhao John S. Tsang Luca Gatt-inoni Nicholas P. Restifo Surgery Branch National Cancer Institute National Institutes of Health Bethesda MD 20892 USA cambridge institute for Medical Research University of Cam bridge Cambridge CB20XY UK Systems Genomics and Bioinformatics Unit Laboratory of Systems Biology National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA department of Environmental Medicine New York University School of Medicine Tuxedo NY 10987 USA Experimental Transplantation and Immunology Branch National Cancer Institute National Institutes of Health Bethesda MD 20892 USA department of Physics The George Washington University Washington DC 20052 USA Research Branch Sidra Medical and Research Centre Doha Qatar Infectious Disease and Immunogenetics Section Department of Transfusion Medicine Clinical Center National Institutes of Health Bethesda MD 20892 USA clinical Investigator Development Program NCI/NIH Bethesda MD 20892 USA Systems biology center National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 20892 USA. Lombardi comprehensive cancer center Georgetown University Washington. DC 20007. United States. Bethesda. MD 20892. USA.

To better elucidate epigenetic mechanisms that correlate with the dynamic gene expression program observed upon T-cell differentiation, we investigated the genomic landscape of histone modifications in naive and memory cD8＋ T cells. Using a chlP-Seq approach coupled with global gene expression profiling, we generated genome-wide histone H3 lysine 4 （H3K4me3） and H3 lysine 27 （H3K27me3） trimethylation maps in naive, T memory stem cells, central memory cells, and effector memory cells in order to gain insight into how histone architecture is remodeled during T cell differentiation. We show that H3K4me3 histone modifications are associated with activation of genes, while H3K27me3 is negatively correlated with gene expression at canonical loci and enhancers associated with T-cell metabolism, effector function, and memory. Our results also reveal histone modifications and gene expression signatures that distinguish the recently identified T memory stem cells from other cD8＋ T-cell subsets. Taken together, our results suggest that cD8＋ lymphocytes undergo chromatin remodeling in a progressive fashion. These findings have major implications for our understanding of peripheral T-cell ontogeny and the formation of immunological memory.

关键词： TRANScRIPTION FAcTOR STEM-cELLS MEMORY EFFEcTOR DIFFERENTIATION BET FATE LYMPHOcYTES MAINTENANcE GENERATION

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