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Reprogramation

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https://www.readbyqxmd.com/read/29791845/equilibrative-nucleoside-transporter-3-regulates-t-cell-homeostasis-by-coordinating-lysosomal-function-with-nucleoside-availability
#1
Chin-Wen Wei, Chia-Ying Lee, Ding-Jin Lee, Chang-Feng Chu, Ju-Chu Wang, Tien-Chiao Wang, Wann-Neng Jane, Zee-Fen Chang, Chuen-Miin Leu, Ivan L Dzhagalov, Chia-Lin Hsu
T cells are a versatile immune cell population responding to challenges by differentiation and proliferation followed by contraction and memory formation. Dynamic metabolic reprogramming is essential for T cells to meet the biosynthetic needs and the reutilization of biomolecules, processes that require active participation of metabolite transporters. Here, we show that equilibrative nucleoside transporter 3 (ENT3) is highly expressed in peripheral T cells and has a key role in maintaining T cell homeostasis by supporting the proliferation and survival of T cells...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29791079/overexpression-of-tet3-in-donor-cells-enhances-goat-somatic-cell-nuclear-transfer-efficiency
#2
Chengquan Han, Ruizhi Deng, Tingchao Mao, Yan Luo, Biao Wei, Peng Meng, Lu Zhao, Qing Zhang, Fusheng Quan, Liu Jun, Yong Zhang
Ten-eleven translocation 3 (TET3) mediates active DNA demethylation of paternal genomes during mouse embryonic development. However, the mechanism of DNA demethylation in goat embryos remains unknown. In addition, aberrant DNA methylation reprogramming prevalently occurs in cloned embryos by somatic cell nuclear transfer (SCNT). In this study, we reported that TET3 is a key factor in DNA demethylation in goat pre-implantation embryos. Knockdown of Tet3 hindered DNA demethylation at 2-4-cell stage in goat embryos and decreased Nanog expression in blastocysts...
May 23, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29789716/xct-slc7a11-mediated-metabolic-reprogramming-promotes-non-small-cell-lung-cancer-progression
#3
Xiangming Ji, Jun Qian, S M Jamshedur Rahman, Peter J Siska, Yong Zou, Bradford K Harris, Megan D Hoeksema, Irina A Trenary, Chen Heidi, Rosana Eisenberg, Jeffrey C Rathmell, Jamey D Young, Pierre P Massion
Many tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29789579/endogenous-authentic-oct4a-proteins-directly-regulate-fos-ap-1-transcription-in-somatic-cancer-cells
#4
Yanwen Zhou, Xinyu Chen, Bo Kang, Shiqi She, Xiaobing Zhang, Cheng Chen, Wenxin Li, Wenjie Chen, Songsong Dan, Xiaoyun Pan, Xiaoli Liu, Jianqin He, Qingwei Zhao, Chenggang Zhu, Ling Peng, Haoyi Wang, Hangping Yao, Hongcui Cao, Lanjuan Li, Meenhard Herlyn, Ying-Jie Wang
OCT4A is well established as a master transcription factor for pluripotent stem cell (PSC) self-renewal and a pioneer factor for initiating somatic cell reprogramming, yet its presence and functionality in somatic cancer cells remain controversial and obscure. By combining the CRISPR-Cas9-based gene editing with highly specific PCR assays, highly sensitive immunoassays, and mass spectrometry, we provide unequivocal evidence here that full-length authentic OCT4A transcripts and proteins were both present in somatic cancer cells, and OCT4A proteins were heterogeneously expressed in the whole cell population and when expressed, they are predominantly localized in cell nucleus...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789206/environmental-signals-influencing-myeloid-cell-metabolism-and-function-in-diabetes
#5
REVIEW
Jacqueline M Ratter, Cees J Tack, Mihai G Netea, Rinke Stienstra
The environment induces metabolic reprogramming of immune cells via specific signaling pathways. Recent studies have revealed that changes in cell metabolism affect key immune cell functions including cytokine production and migration. In diabetes, these functions are either insufficiently or excessively activated, translating into diabetes-associated complications, including increased susceptibility to infection and accelerated cardiovascular disease. Diabetes alters the abundance of environmental signals, including glucose, insulin, and lipids...
May 19, 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29788997/2d-versus-3d-human-induced-pluripotent-stem-cell-derived-cultures-for-neurodegenerative-disease-modelling
#6
REVIEW
Eduarda G Z Centeno, Helena Cimarosti, Angela Bithell
Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results...
May 22, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29788890/inhibition-of-pyruvate-dehydrogenase-kinase-as-a-therapeutic-strategy-against-cancer
#7
Swatishree Sradhanjali, Mamatha M Reddy
Cancer cells alter their metabolism to support the uninterrupted supply of biosynthetic molecules required for continuous proliferation. Glucose metabolism is frequently reprogrammed in several tumors in addition to fatty acid, amino acid and glutamine metabolism. Pyruvate dehydrogenase kinase (PDK) is a gatekeeper enzyme involved in altered glucose metabolism in tumors. There are four isoforms of PDK (1 to 4) in humans. PDK phosphorylates E1α subunit of pyruvate dehydrogenase complex (PDC) and inactivates it...
May 22, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29788888/scap-srebps-are-central-players-in-lipid-metabolism-and-novel-metabolic-targets-in-cancer-therapy
#8
Xiang Cheng, Jianying Li, Deliang Guo
Lipid metabolism reprogramming emerges as a new hallmark of malignancies. Sterol regulatory element-binding proteins (SREBPs), which are central players in lipid metabolism, are endoplasmic reticulum (ER)-bound transcription factors that control the expression of genes important for lipid synthesis and uptake. Their transcriptional activation requires binding to SREBP cleavage-activating protein (SCAP) to translocate their inactive precursors from the ER to the Golgi to undergo cleavage and subsequent nucleus translocation of their NH2-terminal forms...
May 22, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29787979/genome-wide-analysis-reveals-tnfaip8l2-as-an-immune-checkpoint-regulator-of-inflammation-and-metabolism
#9
Ting Li, Wei Wang, Shunyou Gong, Honghong Sun, Huqin Zhang, An-Gang Yang, Youhai H Chen, Xinyuan Li
The interplay between inflammation and metabolism is widely recognized, yet the underlying molecular mechanisms remain poorly characterized. Using experimental database mining and genome-wide gene expression profiling methods, we found that in contrast to other TNFAIP8 family members, TNFAIP8L2 (TIPE2) was preferentially expressed in human myeloid cell types. In addition, Tnfaip8l2 expression drastically decreased in lipopolysaccharide (LPS)-stimulated macrophages. Consequently, Tnfaip8l2 deficiency led to heightened expression of genes that were enriched for leukocyte activation and lipid biosynthesis pathways...
May 19, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29786797/nmr-based-prostate-cancer-metabolomics
#10
Leslie R Euceda, Maria K Andersen, May-Britt Tessem, Siver A Moestue, Maria T Grinde, Tone F Bathen
Prostate cancer is the second most common malignancy, and the fifth leading cause of cancer-related death among men, worldwide. A major unsolved clinical challenge in prostate cancer is the ability to accurately distinguish indolent cancer types from the aggressive ones. Reprogramming of metabolism is now a widely accepted hallmark of cancer development, where cancer cells must be able to convert nutrients to biomass while maintaining energy production. Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues, or organisms...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786657/eukaryotic-translation-initiation-factor-4a-down-regulation-mediates-interleukin-24-induced-apoptosis-through-inhibition-of-translation
#11
Xuelin Zhong, Leah Persaud, Hilal Muharam, Ashleigh Francis, Dibash Das, Bertal Huseyin Aktas, Moira Sauane
Dysregulated activity of helicase eIF4A drives transformation to and maintenance of cancer cell phenotype by reprogramming cellular translation. Interleukin 24 (IL-24) is a tumor-suppressing protein, which has the ability to inhibit angiogenesis, sensitize cancer cells to chemotherapy, and induce cancer cell-specific apoptosis. In this study, we found that eIF4A is inhibited by IL-24. Consequently, selective reduction of translation was observed for mRNAs harboring strong secondary structures in their 5'-untranslated regions (5'UTRs)...
May 22, 2018: Cancers
https://www.readbyqxmd.com/read/29786646/metabolic-reprogramming-by-3-iodothyronamine-t1am-a-new-perspective-to-reverse-obesity-through-co-regulation-of-sirtuin-4-and-6-expression
#12
Fariba M Assadi-Porter, Hannah Reiland, Martina Sabatini, Leonardo Lorenzini, Vittoria Carnicelli, Micheal Rogowski, Ebru S Selen Alpergin, Marco Tonelli, Sandra Ghelardoni, Alessandro Saba, Riccardo Zucchi, Grazia Chiellini
Obesity is a complex disease associated with environmental and genetic factors. 3-Iodothyronamine (T1AM) has revealed great potential as an effective weight loss drug. We used metabolomics and associated transcriptional gene and protein expression analysis to investigate the tissue specific metabolic reprogramming effects of subchronic T1AM treatment at two pharmacological daily doses (10 and 25 mg/kg) on targeted metabolic pathways. Multi-analytical results indicated that T1AM at 25 mg/kg can act as a novel master regulator of both glucose and lipid metabolism in mice through sirtuin-mediated pathways...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786549/pluripotent-stem-cells-induction-and-self-renewal
#13
REVIEW
R Abu-Dawud, N Graffmann, S Ferber, W Wruck, J Adjaye
Pluripotent stem cells (PSCs) lie at the heart of modern regenerative medicine due to their properties of unlimited self-renewal in vitro and their ability to differentiate into cell types representative of the three embryonic germ layers-mesoderm, ectoderm and endoderm. The derivation of induced PSCs bypasses ethical concerns associated with the use of human embryonic stem cells and also enables personalized cell-based therapies. To exploit their regenerative potential, it is essential to have a firm understanding of the molecular processes associated with their induction from somatic cells...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786548/designer-human-tissue-coming-to-a-lab-near-you
#14
David C Hay, Cliona O'Farrelly
Human pluripotent stem cells (PSCs) offer a scalable alternative to primary and transformed human tissue. PSCs include human embryonic stem cells, derived from the inner cell mass of blastocysts unsuitable for human implantation; and induced PSCs, generated by the reprogramming of somatic cells. Both cell types display the ability to self-renew and retain pluripotency, promising an unlimited supply of human somatic cells for biomedical application. A distinct advantage of using PSCs is the ability to select for genetic background, promising personalized modelling of human biology 'in a dish' or immune-matched cell-based therapies for the clinic...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29785785/metabolism-within-the-tumor-microenvironment-and-its-implication-on-cancer-progression-an-ongoing-therapeutic-target
#15
REVIEW
Ma Carmen Ocaña, Beatriz Martínez-Poveda, Ana R Quesada, Miguel Ángel Medina
Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment (TME)...
May 22, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29785028/the-reference-epigenome-and-regulatory-chromatin-landscape-of-chronic-lymphocytic-leukemia
#16
Renée Beekman, Vicente Chapaprieta, Núria Russiñol, Roser Vilarrasa-Blasi, Núria Verdaguer-Dot, Joost H A Martens, Martí Duran-Ferrer, Marta Kulis, François Serra, Biola M Javierre, Steven W Wingett, Guillem Clot, Ana C Queirós, Giancarlo Castellano, Julie Blanc, Marta Gut, Angelika Merkel, Simon Heath, Anna Vlasova, Sebastian Ullrich, Emilio Palumbo, Anna Enjuanes, David Martín-García, Sílvia Beà, Magda Pinyol, Marta Aymerich, Romina Royo, Montserrat Puiggros, David Torrents, Avik Datta, Ernesto Lowy, Myrto Kostadima, Maša Roller, Laura Clarke, Paul Flicek, Xabier Agirre, Felipe Prosper, Tycho Baumann, Julio Delgado, Armando López-Guillermo, Peter Fraser, Marie-Laure Yaspo, Roderic Guigó, Reiner Siebert, Marc A Martí-Renom, Xose S Puente, Carlos López-Otín, Ivo Gut, Hendrik G Stunnenberg, Elias Campo, Jose I Martin-Subero
Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29784957/metabolic-reprogramming-in-leaf-lettuce-grown-under-different-light-quality-and-intensity-conditions-using-narrow-band-leds
#17
Kazuyoshi Kitazaki, Atsushi Fukushima, Ryo Nakabayashi, Yozo Okazaki, Makoto Kobayashi, Tetsuya Mori, Tomoko Nishizawa, Sebastian Reyes-Chin-Wo, Richard W Michelmore, Kazuki Saito, Kazuhiro Shoji, Miyako Kusano
Light-emitting diodes (LEDs) are an artificial light source used in closed-type plant factories and provide a promising solution for a year-round supply of green leafy vegetables, such as lettuce (Lactuca sativa L.). Obtaining high-quality seedlings using controlled irradiation from LEDs is critical, as the seedling health affects the growth and yield of leaf lettuce after transplantation. Because key molecular pathways underlying plant responses to a specific light quality and intensity remain poorly characterised, we used a multi-omics-based approach to evaluate the metabolic and transcriptional reprogramming of leaf lettuce seedlings grown under narrow-band LED lighting...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29784918/early-lineage-segregation-of-multipotent-embryonic-mammary-gland-progenitors
#18
Aline Wuidart, Alejandro Sifrim, Marco Fioramonti, Shigeru Matsumura, Audrey Brisebarre, Daniel Brown, Alessia Centonze, Anne Dannau, Christine Dubois, Alexandra Van Keymeulen, Thierry Voet, Cédric Blanpain
The mammary gland is composed of basal cells and luminal cells. It is generally believed that the mammary gland arises from embryonic multipotent progenitors, but it remains unclear when lineage restriction occurs and what mechanisms are responsible for the switch from multipotency to unipotency during its morphogenesis. Here, we perform multicolour lineage tracing and assess the fate of single progenitors, and demonstrate the existence of a developmental switch from multipotency to unipotency during embryonic mammary gland development...
May 21, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29784817/topography-of-epithelial-mesenchymal-plasticity
#19
Francesc Font-Clos, Stefano Zapperi, Caterina A M La Porta
The transition between epithelial and mesenchymal states has fundamental importance for embryonic development, stem cell reprogramming, and cancer progression. Here, we construct a topographic map underlying epithelial-mesenchymal transitions using a combination of numerical simulations of a Boolean network model and the analysis of bulk and single-cell gene expression data. The map reveals a multitude of metastable hybrid phenotypic states, separating stable epithelial and mesenchymal states, and is reminiscent of the free energy measured in glassy materials and disordered solids...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784665/srebf1-activity-is-regulated-by-an-ar-mtor-nuclear-axis-in-prostate-cancer
#20
Etienne Audet-Walsh, Mathieu Vernier, Tracey Yee, Chloe E Laflamme, Susan Li, Yonghong Chen, Vincent Giguere
Reprogramming of cellular metabolism is an important feature of prostate cancer (PCa), including altered lipid metabolism. Recently, it was observed that the nuclear fraction of mTOR is essential for the androgen-mediated metabolic reprogramming of PCa cells. Herein, it is demonstrated that the androgen receptor (AR) and mTOR bind to regulatory regions of sterol regulatory element binding transcription factor 1 (SREBF1) to control its expression, while dual activation of these signaling pathways also promotes SREBF1 cleavage and its translocation to the nucleus...
May 21, 2018: Molecular Cancer Research: MCR
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