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https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#1
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28634176/impact-of-glycemic-variability-on-chromatin-remodeling-oxidative-stress-and-endothelial-dysfunction-in-type-2-diabetic-patients-with-target-hba1c-levels
#2
Sarah Costantino, Francesco Paneni, Rodolfo Battista, Lorenzo Castello, Giuliana Capretti, Sergio Chiandotto, Luigi Tanese, Giulio Russo, Dario Pitocco, Gaetano A Lanza, Massimo Volpe, Thomas F Lüscher, Francesco Cosentino
Intensive glycemic control (IGC) targeting HbA1c fails to show an unequivocal reduction of macrovascular complications in type 2 diabetes (T2D), however the underlining mechanisms remain elusive. Epigenetic changes are emerging as important mediators of cardiovascular damage and may play a role in this setting. This study investigates whether epigenetic regulation of the adaptor protein p66(Shc), a key driver of mitochondrial oxidative stress, contributes to persistent vascular dysfunction in T2D patients despite IGC...
June 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28628607/host-gene-expression-analysis-in-sri-lankan-melioidosis-patients
#3
Shivankari Krishnananthasivam, Nimanthi Jayathilaka, Harindra Darshana Sathkumara, Enoka Corea, Mohan Natesan, Aruna Dharshan De Silva
BACKGROUND: Melioidosis is a life threatening infectious disease caused by the gram-negative bacillus Burkholderia pseudomallei predominantly found in southeast Asia and northern Australia. Studying the host transcription profiles in response to infection is crucial for understanding disease pathogenesis and correlates of disease severity, which may help improve therapeutic intervention and survival. The aim of this study was to analyze gene expression levels of human host factors in melioidosis patients and establish useful correlation with disease biomarkers, compared to healthy individuals and patients with sepsis caused by other pathogens...
June 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28614801/dna-methyltransferase-3b-regulates-articular-cartilage-homeostasis-by-altering-metabolism
#4
Jie Shen, Cuicui Wang, Daofeng Li, Taotao Xu, Jason Myers, John M Ashton, Ting Wang, Michael J Zuscik, Audrey McAlinden, Regis J O'Keefe
Osteoarthritis (OA) is the most common form of arthritis worldwide. It is a complex disease affecting the whole joint but is generally characterized by progressive degradation of articular cartilage. Recent genome-wide association screens have implicated distinct DNA methylation signatures in OA patients. We show that the de novo DNA methyltransferase (Dnmt) 3b, but not Dnmt3a, is present in healthy murine and human articular chondrocytes and its expression decreases in OA mouse models and in chondrocytes from human OA patients...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28614398/5-aza-2-deoxycytidine-in-the-medial-prefrontal-cortex-regulates-alcohol-related-behavior-and-ntf3-trkc-expression-in-rats
#5
Xiaomeng Qiao, Fangyuan Yin, Yuanyuan Ji, Yunxiao Li, Peng Yan, Jianghua Lai
Recent studies have indicated that DNA methylation plays an important role in the development of alcohol abuse. 5-Aza-2'-deoxycytidine (5-Aza-dc), an inhibitor of DNA methyltransferases, was FDA approved for myelodysplastic syndrome treatment. However, it is unclear whether 5-Aza-dc is involved in alcohol abuse. In this study, using a chronic alcohol exposure model in rats, 5-Aza-dc was injected into the medial prefrontal cortex (mPFC). Alcohol-drinking behavior and the anxiety related behavior were evaluated by two-bottle choice and open field test...
2017: PloS One
https://www.readbyqxmd.com/read/28607593/chemoresistance-of-colorectal-cancer-to-5-fluorouracil-is-associated-with-silencing-of-the-bnip3-gene-through-aberrant-methylation
#6
Jianming He, Li Pei, Heng Jiang, Weiwen Yang, Jianfang Chen, Houjie Liang
Purpose To investigate the correlation between chemoresistance of colorectal cancer to 5-fluorouracil and BNIP3 and the underlying mechanism. Methods BNIP3 protein in specimens was evaluated using immunohistochemistry. Semi-quantitative reverse transcription PCR and Western blot was employed to assay gene expression. The promoter methylation status of BNIP3 was examined by methylation-specific PCR. Drug sensitivity was assayed using MTT assay. Results Specimens from 81 patients with colorectal cancer receiving 5-fluorouracil-based chemotherapy were analyzed...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28607180/p53-is-essential-for-dna-methylation-homeostasis-in-na%C3%A3-ve-embryonic-stem-cells-and-its-loss-promotes-clonal-heterogeneity
#7
Ayala Tovy, Adam Spiro, Ryan McCarthy, Zohar Shipony, Yael Aylon, Kendra Alton, Elena Ainbinder, Noa Furth, Amos Tanay, Michelle Barton, Moshe Oren
DNA methylation is a key regulator of embryonic stem cell (ESC) biology, dynamically changing between naïve, primed, and differentiated states. The p53 tumor suppressor is a pivotal guardian of genomic stability, but its contributions to epigenetic regulation and stem cell biology are less explored. We report that, in naïve mouse ESCs (mESCs), p53 restricts the expression of the de novo DNA methyltransferases Dnmt3a and Dnmt3b while up-regulating Tet1 and Tet2, which promote DNA demethylation. The DNA methylation imbalance in p53-deficient (p53(-/-)) mESCs is the result of augmented overall DNA methylation as well as increased methylation landscape heterogeneity...
June 12, 2017: Genes & Development
https://www.readbyqxmd.com/read/28593035/smchd1-regulates-a-limited-set-of-gene-clusters-on-autosomal-chromosomes
#8
Amanda G Mason, Roderick C Slieker, Judit Balog, Richard J L F Lemmers, Chao-Jen Wong, Zizhen Yao, Jong-Won Lim, Galina N Filippova, Enrico Ne, Rabi Tawil, Bas T Heijmans, Stephen J Tapscott, Silvère M van der Maarel
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is in most cases caused by a contraction of the D4Z4 macrosatellite repeat on chromosome 4 (FSHD1) or by mutations in the SMCHD1 or DNMT3B gene (FSHD2). Both situations result in the incomplete epigenetic repression of the D4Z4-encoded retrogene DUX4 in somatic cells, leading to the aberrant expression of DUX4 in the skeletal muscle. In mice, Smchd1 regulates chromatin repression at different loci, having a role in CpG methylation establishment and/or maintenance...
2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28591566/regulation-of-clustered-protocadherin-genes-in-individual-neurons
#9
REVIEW
Teruyoshi Hirayama, Takeshi Yagi
Individual neurons are basic functional units in the complex system of the brain. One aspect of neuronal individuality is generated by stochastic and combinatorial expression of diverse clustered protocadherins (Pcdhs), encoded by the Pcdha, Pcdhb, and Pcdhg gene clusters, that are critical for several aspects of neural circuit formation. Each clustered Pcdh gene has its own promoter containing conserved sequences and is transcribed by a promoter choice mechanism involving interaction between the promoter and enhancers...
June 4, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28587678/smchd1-regulates-a-limited-set-of-gene-clusters-on-autosomal-chromosomes
#10
Amanda G Mason, Roderick C Slieker, Judit Balog, Richard J L F Lemmers, Chao-Jen Wong, Zizhen Yao, Jong-Won Lim, Galina N Filippova, Enrico Ne, Rabi Tawil, Bas T Heijmans, Stephen J Tapscott, Silvère M van der Maarel
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is in most cases caused by a contraction of the D4Z4 macrosatellite repeat on chromosome 4 (FSHD1) or by mutations in the SMCHD1 or DNMT3B gene (FSHD2). Both situations result in the incomplete epigenetic repression of the D4Z4-encoded retrogene DUX4 in somatic cells, leading to the aberrant expression of DUX4 in the skeletal muscle. In mice, Smchd1 regulates chromatin repression at different loci, having a role in CpG methylation establishment and/or maintenance...
June 6, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28587163/a-tox21-approach-to-altered-epigenetic-landscapes-assessing-epigenetic-toxicity-pathways-leading-to-altered-gene-expression-and-oncogenic-transformation-in-vitro
#11
REVIEW
Craig L Parfett, Daniel Desaulniers
An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs...
June 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28583846/epigenetic-effects-of-inhibition-of-heat-shock-protein-90-hsp90-in-human-pancreatic-and-colon-cancer
#12
Ganji Purnachandra Nagaraju, Christina Wu, Neha Merchant, Zhengjia Chen, Gregory B Lesinski, Bassel F El-Rayes
Silencing of tumor suppressor and DNA repair genes through methylation plays a role in cancer development, growth and response to therapy in colorectal and pancreatic cancers. Heat shock protein 90 (HSP90) regulates transcription of DNA methyltransferase enzymes (DNMT). In addition, DNMTs are client proteins of HSP90. The aim of this study is to evaluate the effects of HSP90 inhibition on DNA methylation in colorectal and pancreatic cancer cell lines. Our data shows that inhibition of HSP90 using ganetespib resulted in downregulation of mRNA and protein expression of DNMT1, DNMT3A, and DNMT3B in HT-29 and MIA PaCa-2 cell lines...
June 3, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28579430/cry2-is-suppressed-by-foxm1-mediated-promoter-hypermethylation-in-breast-cancer
#13
Lingling Liu, Hong Shen, Yang Wang
Loss of CRY2 confers aggressive phenotypes to breast cancer. However, the mechanism of its downregulation and its prognostic value in breast cancer are still not clear. Our data mining in TCGA breast cancer cohort (TCGA-BRCA) showed that the luminal A subtype of breast cancer had the highest CRY2 expression, while the basal-like subtype had the lowest CRY2 expression. The ER+ group had significantly higher CRY2 expression than the ER- group. Demethylation treatment using 5-AZA-dC significantly restored CRY2 expression in MDA-MB-231 and BT549 cells...
June 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28578488/17%C3%AE-estradiol-increases-non-cpg-methylation-in-exon-1-of-the-rainbow-trout-oncorhynchus-mykiss-myod-gene
#14
Prasanthi P Koganti, Jian Wang, Beth Cleveland, Jianbo Yao
MyoD is an important myogenic transcription factor necessary for the differentiation of myogenic precursor cells (MPC) to form mature myotubes, a process essential for muscle growth. Epigenetic markers such as CpH methylation are known gene regulators that are important for the differentiation process. In this study, we investigated whether DNA methylation is a potential mechanism associated with the ability of 17β-estradiol (E2) to reduce MyoD gene expression and muscle growth in rainbow trout. Rainbow trout received a single intraperitoneal injection of E2 or the injection vehicle (control)...
June 3, 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28560437/the-expression-of-dna-methyltransferases3a-is-specifically-downregulated-in-chorionic-villi-of-early-embryo-growth-arrest-cases
#15
Huating Gu, Jing Gao, Weiwei Guo, Yu Zhou, Qingnuan Kong
The aim of the present study was to investigate the expression pattern of four DNA methyltransferases (DNMT1, DNMT3A, DNMT3B and DNMT3L) in placenta chorionic villi of early embryo growth arrest patients. Chorionic villous specimens were obtained from 40 pregnant patients diagnosed with early embryo growth arrest and 40 healthy women who underwent selective pregnancy termination. Reverse transcription‑quantitative polymerase chain reaction, immunohistochemistry and western blot analysis were performed to characterize the mRNA and protein expression of DNMTs in chorionic villous cells...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28502886/hmga2-a-driver-of-inflammation-is-associated-with-hypermethylation-in-acute-liver-injury
#16
Huimin Huang, Haidi Li, Xin Chen, Yang Yang, Xiaofeng Li, Wanxia Li, Cheng Huang, Xiaoming Meng, Lei Zhang, Jun Li
Acute liver injury (ALI) is characteristic of abrupt hepatic dysfunction and inflammatory response. Activaion of Kupffer cells (KCs) plays a central role in the pathogenesis of ALI. Since the High Mobility Group A protein2 (HMGA2) occurs as a driver at critical stage of hepatocellular carcinoma, herein, we investigated the role of HMGA2 in macrophage activation during ALI. Our study found that the expression of HMGA2 decreased dramatically both in KCs isolated from the liver in mice with ALI and in LPS-induced RAW264...
August 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28491150/dynamic-silencing-of-somatic-l1-retrotransposon-insertions-reflects-the-developmental-and-cellular-contexts-of-their-genomic-integration
#17
Manoj Kannan, Jingfeng Li, Sarah E Fritz, Kathryn E Husarek, Jonathan C Sanford, Teresa L Sullivan, Pawan Kumar Tiwary, Wenfeng An, Jef D Boeke, David E Symer
BACKGROUND: The ongoing mobilization of mammalian transposable elements (TEs) contributes to natural genetic variation. To survey the epigenetic control and expression of reporter genes inserted by L1 retrotransposition in diverse cellular and genomic contexts, we engineered highly sensitive, real-time L1 retrotransposon reporter constructs. RESULTS: Here we describe different patterns of expression and epigenetic controls of newly inserted sequences retrotransposed by L1 in various somatic cells and tissues including cultured human cancer cells, mouse embryonic stem cells, and tissues of pseudofounder transgenic mice and their progeny...
2017: Mobile DNA
https://www.readbyqxmd.com/read/28484495/mitochondrial-dna-hypomethylation-is-a-biomarker-associated-with-induced-senescence-in-human-fetal-heart-mesenchymal-stem-cells
#18
Dehai Yu, Zhonghua Du, Lingling Pian, Tao Li, Xue Wen, Wei Li, Su-Jeong Kim, Jialin Xiao, Pinchas Cohen, Jiuwei Cui, Andrew R Hoffman, Ji-Fan Hu
Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs) from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28480311/strip2-is-indispensable-for-the-onset-of-embryonic-stem-cell-differentiation
#19
Davood Sabour, Sureshkumar Perumal Srinivasan, Susan Rohani, Vilas Wagh, John Antonydas Gaspar, Darius Panek, Mostafa Abootorabi Ardestani, Michael Xavier Doss, Nicole Riet, Hinrich Abken, Jürgen Hescheler, Symeon Papadopoulos, Agapios Sachinidis
The role of striatin interacting protein 2 (Strip2) in differentiation of embryonic stem cells (ESCs) is still under debate. Strip2-silenced murine (KD) ESCs were differentiated for 4, 8, 12, and 16 days. We show that Strip2 is distributed in the perinucleus or nuclei of wild-type (WT) undifferentiated ESCs, but is localized in high-density nuclear bodies in differentiated cells. CellNet analysis of microarray gene expression data for the KD and scrambled control (SCR) embryoid bodies (EBs), as well as immunostainings of key pluripotent factors, demonstrated that differentiation of KD ESCs is repressed...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28465359/elevated-foxg1-and-sox2-in-glioblastoma-enforces-neural-stem-cell-identity-through-transcriptional-control-of-cell-cycle-and-epigenetic-regulators
#20
Harry Bulstrode, Ewan Johnstone, Maria Angeles Marques-Torrejon, Kirsty M Ferguson, Raul Bardini Bressan, Carla Blin, Vivien Grant, Sabine Gogolok, Ester Gangoso, Sladjana Gagrica, Christine Ender, Vassiliki Fotaki, Duncan Sproul, Paul Bertone, Steven M Pollard
Glioblastoma multiforme (GBM) is an aggressive brain tumor driven by cells with hallmarks of neural stem (NS) cells. GBM stem cells frequently express high levels of the transcription factors FOXG1 and SOX2. Here we show that increased expression of these factors restricts astrocyte differentiation and can trigger dedifferentiation to a proliferative NS cell state. Transcriptional targets include cell cycle and epigenetic regulators (e.g., Foxo3, Plk1, Mycn, Dnmt1, Dnmt3b, and Tet3). Foxo3 is a critical repressed downstream effector that is controlled via a conserved FOXG1/SOX2-bound cis-regulatory element...
April 15, 2017: Genes & Development
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