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  • Cell Research
    of Stomatology 22 Zhongguancun South Avenue Beijing 100081 China 2 Center for Craniofacial Molecular Biology Ostrow School of Dentistry University of Southern California 2250 Alcazar Street CSA 103 Los Angeles CA 90033 USA 3 National Institute of Dental and Craniofacial Research National Institutes of Health Bethesda MD 20892 2190 USA Correspondence Songtao Shi Yanheng Zhou Tel 323 442 3038 86 10 82195381 E mail songtaos usc edu yanhengzhou gmail com Bone marrow mesenchymal stem cells MSCs comprise a heterogeneous population of postnatal progenitor cells with profound immunomodulatory properties such as upregulation of Foxp3 regulatory T cells Tregs and downregulation of Th17 cells However it is unknown whether different MSC subpopulations possess the same range of immunomodulatory function Here we show that a subset of single colony derived MSCs producing IL 17 is different from bulk MSC population in that it cannot upregulate Tregs downregulate Th17 cells or ameliorate disease phenotypes in a colitis mouse model Mechanistically we reveal that IL 17 produced by these MSCs activates the NFκB pathway to downregulate TGF β production in MSCs resulting in abolishment of MSC based immunomodulation Furthermore we show that NFκB is able to directly bind to TGF β promoter region to regulate

    Original URL path: http://www.cell-research.com/arts.asp?id=60 (2016-02-14)
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  • Cell Research
    Histone H3K27me3 demethylases KDM6A and KDM6B modulate definitive endoderm differentiation from human ESCs by regulating WNT signaling pathway Wei Jiang 1 2 Jinzhao Wang 1 2 and Yi Zhang 1 2 1 Howard Hughes Medical Institute Chevy Chase Maryland 20815 6789 USA 2 Department of Biochemistry and Biophysics Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill Chapel Hill NC 27599 7295 USA Correspondence Yi Zhang Tel 1 919 843 8225 E mail yi zhang med unc edu Definitive endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver However whether epigenetic regulation contributes to this process is unknown Here we show that the H3K27me3 demethylases KDM6A and KDM6B play an important role in endoderm differentiation from human ESCs Knockdown of KDM6A or KDM6B impairs endoderm differentiation which can be rescued by sequential treatment with WNT agonist and antagonist KDM6A and KDM6B contribute to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesendoderm and definitive endoderm differentiation respectively Our study not only uncovers an important role of the H3K27me3 demethylases in definitive endoderm differentiation but also reveals that they achieve this through modulating the WNT

    Original URL path: http://www.cell-research.com/arts.asp?id=61 (2016-02-14)
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  • Cell Research
    Xie 1 2 1 Laboratory of Receptor based Bio medicine Shanghai Key Laboratory of Signaling and Disease Research School of Life Sciences and Technology Tongji University Shanghai 200092 China 2 Stake Key Laboratory of Drug Research the National Center for Drug Screening Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China Correspondence Xin Xie Tel 86 21 50801313 ex 156 E mail xxie mail shcnc ac cn Environmental stress mediated adaptation plays essential roles in the evolution of life Cellular adaptation mechanisms usually involve the regulation of chromatin structure transcription mRNA stability and translation which eventually lead to efficient changes in gene expression Global epigenetic change is also involved in the reprogramming of somatic cells into induced pluripotent stem iPS cells by defined factors Here we report that environmental stress such as hyperosmosis not only facilitates four factor mediated reprogramming but also enhances two or one factor induced iPS cell generation Hyperosmosis induced p38 activation plays a critical role in this process Constitutive active p38 mimics the positive effect of hyperosmosis while dominant negative p38 and p38 inhibitor block the effect of hyperosmosis Further study indicates stress mediated p38 activation may promote reprogramming by reducing the global

    Original URL path: http://www.cell-research.com/arts.asp?id=62 (2016-02-14)
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  • Cell Research
    Houqi Liu 2 Cizhong Jiang 1 1 Clinical and Translational Research Center of Shanghai First Maternity Infant Health Hospital Shanghai Key Laboratory of Signaling and Disease Research School of Life Science and Technology Tongji University 1239 Siping Road Shanghai 200092 China 2 Department of Embryology and Histology Second Military Medical University Shanghai 200433 China Correspondence Jiuhong Kang Tel 086 21 65988876 E mail jhkang tongji edu cn Fibroblasts can be reprogrammed into induced pluripotent stem cells iPSCs by the application of Yamanaka factors OSKM but the mechanisms underlying this reprogramming remain poorly understood Here we report that Sox2 directly regulates endogenous microRNA 29b miR 29b expression during iPSC generation and that miR 29b expression is required for OSKM and OSK mediated reprogramming Mechanistic studies show that Dnmt3a and Dnmt3b are in vivo targets of miR 29b and that Dnmt3a and Dnmt3b expression is inversely correlated with miR 29b expression during reprogramming Moreover the effect of miR 29b on reprogramming can be blocked by Dnmt3a or Dnmt3b overexpression Further experiments indicate that miR 29b DNMT signaling is significantly involved in the regulation of DNA methylation related reprogramming events such as mesenchymal to epithelial transition MET and Dlk1 Dio3 region transcription Thus

    Original URL path: http://www.cell-research.com/arts.asp?id=63 (2016-02-14)
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  • Cell Research
    Song Chen 1 2 Shuguang Duo 1 Chengang Xiang 1 3 Jun Jia 1 3 Mina Guo 1 Wei Lai 4 Shichun Lu 4 and Hongkui Deng 1 2 3 1 Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education College of Life Sciences Peking University Beijing 100871 China 2 Center for Life Sciences Peking University Beijing 100871 China 3 Laboratory of Chemical Genomics Shenzhen Graduate School

    Original URL path: http://www.cell-research.com/arts.asp?id=64 (2016-02-14)
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  • Cell Research
    Guangzhou Institutes of Biomedicine and Health Guangzhou Guangdong 510530 China 2 School of Life Sciences University of Science and Technology of China Hefei Anhui 230027 China 3 College of Animal Sciences Stem Cell and Developmental Biology Research Center Zhejiang University Hangzhou Zhejiang 310058 China 4 Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China 5 BGI Shenzhen Shenzhen Guangdong 518083 China 6 BGI Ark Biotechnology Co Ltd Shenzhen Guangdong 518083 China 7 Department of Cell Biology and Genetics College of Life Sciences Nankai University Tianjin 300071 China 8 State Key Laboratory of Agrobiotechnology College of Biological Sciences China Agricultural University Beijing 100193 China 9 Institute of Zoology Chinese Academy of Sciences Beijing 100101 China 10 Department of Gene and Cell Engineering Institute of Animal Sciences Chinese Academy of Agricultural Sciences Beijing 100193 China 11 Central Queensland University Bruce Highway Rockhampton QLD 4702 Australia 12 College of Animal Science and Veterinary Medicine Jilin University Changchun Jilin 130062 China 13 Department of Animal Biotechnology College of Veterinary Medicine Northwest A F University Yangling Shaanxi 712100 China 14 Department of Laboratory Animal Sciences College of Basic medicine Third Military Medical University Chongqing 400038 China

    Original URL path: http://www.cell-research.com/arts.asp?id=65 (2016-02-14)
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  • Cell Research
    Cell Biology CAS Center for Excellence in Molecular Cell Science Institute of Health Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai JiaoTong University School of Medicine Shanghai 200031 China 2 School of Life Sciences and Technology Tongji University Shanghai 200092 China 3 Laboratory of Molecular Developmental Biology Shanghai JiaoTong University School of Medicine Shanghai 200025 China 4 University of Chinese Academy of Sciences Beijing 100049 China Correspondence Ying Jin Tel 86 21 54923342 E mail yjin sibs ac cn Yong Zhang Tel 86 21 65981196 E mail yzhang tongji edu cn SOX2 is a key regulator of multiple types of stem cells especially embryonic stem cells ESCs and neural progenitor cells NPCs Understanding the mechanism underlying the function of SOX2 is of great importance for realizing the full potential of ESCs and NPCs Here through genome wide comparative studies we show that SOX2 executes its distinct functions in human ESCs hESCs and hESC derived NPCs hNPCs through cell type and stage dependent transcription programs Importantly SOX2 suppresses non neural lineages in hESCs and regulates neurogenesis from hNPCs by inhibiting canonical Wnt signaling In hESCs SOX2 achieves such inhibition by direct transcriptional regulation of important Wnt signaling modulators

    Original URL path: http://www.cell-research.com/aoparts.asp?id=465 (2016-02-14)
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  • Cell Research
    1 3 1 Centre for Cancer Research Hudson Institute of Medical Research 27 31 Wright St Clayton Victoria 3168 Australia 2 Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research 27 31 Wright St Clayton Victoria 3168 Australia 3 Department of Molecular and Translational Science Monash University Clayton Victoria 3168 Australia 4 Chicago Genomics Facility University of Chicago IL 60637 USA Correspondence Anthony J Sadler Tel 61 3 8572 2722 Fax 61 3 9594 7167 E mail anthony sadler hudson org au The protein kinase R PKR functions in the antiviral response by controlling protein translation and inflammatory cell signaling pathways We generated a transgenic knock in mouse in which the endogenous PKR is expressed with a point mutation that ablates its kinase activity This novel animal allows us to probe the kinase dependent and independent functions of PKR We used this animal together with a previously generated transgenic mouse that is ablated for PKR expression to determine the role of PKR in regulating the activity of the cryopyrin inflammasome Our data demonstrate that in contradiction to earlier reports PKR represses cryopyrin inflammasome activity We demonstrate that this control is mediated through the established function of PKR

    Original URL path: http://www.cell-research.com/aoparts.asp?id=464 (2016-02-14)
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