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Cellular Reprogramming

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https://www.readbyqxmd.com/read/28650429/acetate-mediated-novel-survival-strategy-against-drought-in-plants
#1
Jong-Myong Kim, Taiko Kim To, Akihiro Matsui, Keitaro Tanoi, Natsuko I Kobayashi, Fumio Matsuda, Yoshiki Habu, Daisuke Ogawa, Takuya Sakamoto, Sachihiro Matsunaga, Khurram Bashir, Sultana Rasheed, Marina Ando, Hiroko Takeda, Kanako Kawaura, Miyako Kusano, Atsushi Fukushima, Takaho A Endo, Takashi Kuromori, Junko Ishida, Taeko Morosawa, Maho Tanaka, Chieko Torii, Yumiko Takebayashi, Hitoshi Sakakibara, Yasunari Ogihara, Kazuki Saito, Kazuo Shinozaki, Alessandra Devoto, Motoaki Seki
Water deficit caused by global climate changes seriously endangers the survival of organisms and crop productivity, and increases environmental deterioration(1,2). Plants' resistance to drought involves global reprogramming of transcription, cellular metabolism, hormone signalling and chromatin modification(3-8). However, how these regulatory responses are coordinated via the various pathways, and the underlying mechanisms, are largely unknown. Herein, we report an essential drought-responsive network in which plants trigger a dynamic metabolic flux conversion from glycolysis into acetate synthesis to stimulate the jasmonate (JA) signalling pathway to confer drought tolerance...
June 26, 2017: Nature Plants
https://www.readbyqxmd.com/read/28649654/cell-state-plasticity-stem-cells-emt-and-the-generation-of-intra-tumoral-heterogeneity
#2
Geoffrey M Wahl, Benjamin T Spike
Cellular heterogeneity in cancer represents a significant challenge. In order to develop effective and lasting therapies, it is essential to understand the source of this heterogeneity, and its role in tumor progression and therapy resistance. Here, we consider not only genetic and epigenetic mechanisms, but also inflammation and cell state reprogramming in creating tumor heterogeneity. We discuss similarities between normal mammary epithelial developmental states and various breast cancer molecular sub-types, and the cells that are thought to propagate them...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28647433/targeted-release-of-transcription-factors-for-human-cell-reprogramming-by-zebra-cell-penetrating-peptide
#3
Benjamin Caulier, Lionel Berthoin, Helène Coradin, Frédéric Garban, Marie Claire Dagher, Benoît Polack, Bertrand Toussaint, Jean Luc Lenormand, David Laurin
Transcription factors (TFs) are key actors of the control of gene expression and consequently of every major process within cells, ranging from cell fate determination, cell cycle control and response to environment. Their ectopic expression has proven high potential in reprogramming cells for regenerative medicine; ontogenesis studies and cell based modelling. Direct delivery of proteins could represent an alternative to current reprogramming methods using gene transfer but still needs technological improvements...
June 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28646660/towards-understanding-transcriptional-networks-in-cellular-reprogramming
#4
REVIEW
Jaber Firas, Jose M Polo
Most of the knowledge we have on the molecular mechanisms of transcription factor mediated reprogramming comes from studies conducted in induced pluripotency. Recently however, a few studies investigated the mechanisms of cellular reprogramming in direct and indirect transdifferentiation, which allows us to explore whether shared parallel mechanisms can be drawn. Moreover, there are currently several computational tools that have been developed to predict and enhance the reprogramming process by reconstructing the transcriptional networks of reprogramming cells...
June 21, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28641785/acute-detachment-of-hexokinase-ii-from-mitochondria-modestly-increases-oxygen-consumption-of-the-intact-mouse-heart
#5
Rianne Nederlof, Simone Denis, Benjamin Lauzier, Christine Des Rosiers, Markku Laakso, Jacob Hagen, Carmen Argmann, Ronald Wanders, Riekelt H Houtkooper, Markus W Hollmann, Sander M Houten, Coert J Zuurbier
OBJECTIVE: Cardiac hexokinase II (HKII) can translocate between cytosol and mitochondria and change its cellular expression with pathologies such as ischemia-reperfusion, diabetes and heart failure. The cardiac metabolic consequences of these changes are unknown. Here we measured energy substrate utilization in cytosol and mitochondria using stabile isotopes and oxygen consumption of the intact perfused heart for 1) an acute decrease in mitochondrial HKII (mtHKII), and 2) a chronic decrease in total cellular HKII...
July 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28640975/nac-transcription-factor-jungbrunnen1-enhances-drought-tolerance-in-tomato
#6
Venkatesh P Thirumalaikumar, Vikas Devkar, Nikolay Mehterov, Shawkat Ali, Rengin Ozgur, Ismail Turkan, Bernd Mueller-Roeber, Salma Balazadeh
Water deficit (drought stress) massively restricts plant growth and the yield of crops; reducing the deleterious effects of drought is therefore of high agricultural relevance. Drought triggers diverse cellular processes including the inhibition of photosynthesis, the accumulation of cell-damaging reactive oxygen species, and gene expression reprogramming, besides others. Transcription factors (TF) are central regulators of transcriptional reprogramming and expression of many TF genes is affected by drought, including members of the NAC family...
June 22, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28637872/hydrogen-sulfide-modulates-eukaryotic-translation-initiation-factor-2%C3%AE-eif2%C3%AE-phosphorylation-status-in-the-integrated-stress-response-pathway
#7
Vinita Yadav, Xing-Huang Gao, Belinda Willard, Maria Hatzoglou, Ruma Banerjee, Omer Kabil
Hydrogen sulfide (H2S) regulates various physiological processes including neuronal activity, vascular tone, inflammation, and energy metabolism. Moreover, H2S elicits cytoprotective effects against stressors in various cellular models of injury. However, the mechanism of the signaling pathways mediating the cytoprotective functions of H2S is not well understood. We previously uncovered a heme-dependent metabolic switch for transient induction of H2S production in the transsulfuration pathway. Here, we demonstrate that increased endogenous H2S production or its exogenous administration modulates major components of the integrated stress response (ISR) promoting a metabolic state primed for stress response...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28634230/similarity-in-gene-regulatory-networks-suggests-that-cancer-cells-share-characteristics-of-embryonic-neural-cells
#8
Zan Zhang, Anhua Lei, Liyang Xu, Lu Chen, Yonglong Chen, Xuena Zhang, Yan Gao, Xiaoli Yang, Min Zhang, Ying Cao
Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and re-differentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that, inhibition of the epigenetic modification enzymes enhancer of zeste homolog 2 (EZH2), histone deacetylases (HDACs) 1 and 3, lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28633080/disruptive-non-disruptive-applications-of-crispr-cas9
#9
REVIEW
Jonathan L Schmid-Burgk
The bacterial type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR Associated (Cas) systems, and in particular Streptococcus pyogenes CRISPR-Cas9, have been broadly applied to edit the genome of bacterial and eukaryotic cells. Cas9, which is an RNA-guided programmable nuclease, is a powerful tool for disrupting protein-coding genes. Cas9 cleaves target sites to generate a double-strand break (DSB) that is repaired via an error-prone repair process, leading to insertion/deletion mutations and gene knockouts...
June 17, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28632775/unique-cellular-interactions-between-pancreatic-cancer-cells-and-the-omentum
#10
Valerya Feygenzon, Shelly Loewenstein, Nir Lubezky, Metsada Pasmanic-Chor, Osnat Sher, Joseph M Klausner, Guy Lahat
Pancreatic cancer is a common cause of cancer-related mortality. Omental spread is frequent and usually represents an ominous event, leading to patient death. Omental metastasis has been studied in ovarian cancer, but data on its role in pancreatic cancer are relatively scarce and the molecular biology of this process has yet to be explored. We prepared tissue explants from human omental fat, and used conditioned medium from the explants for various in vitro and in vivo experiments designed to evaluate pancreatic cancer development, growth, and survival...
2017: PloS One
https://www.readbyqxmd.com/read/28632762/dot1l-inhibitor-improves-early-development-of-porcine-somatic-cell-nuclear-transfer-embryos
#11
Jia Tao, Yu Zhang, Xiaoyuan Zuo, Renyun Hong, Hui Li, Xing Liu, Weiping Huang, Zubing Cao, Yunhai Zhang
Incomplete epigenetic reprogramming of the genome of donor cells causes poor early and full-term developmental efficiency of somatic cell nuclear transfer (SCNT) embryos. Previous research indicate that inhibition of the histone H3 K79 methyltransferase DOT1L, using a selective pharmacological inhibitor EPZ004777 (EPZ), significantly improved reprogramming efficiency during the generation of mouse induced pluripotent stem cells. However, the roles of DOT1L in porcine nuclear transfer-mediated cellular reprogramming are not yet known...
2017: PloS One
https://www.readbyqxmd.com/read/28630930/real-time-quantitative-analysis-of-metabolic-flux-in-live-cells-using-a-hyperpolarized-micromagnetic-resonance-spectrometer
#12
Sangmoo Jeong, Roozbeh Eskandari, Sun Mi Park, Julio Alvarez, Sui Seng Tee, Ralph Weissleder, Michael G Kharas, Hakho Lee, Kayvan R Keshari
Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or "fluxes" of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact cells or organisms, magnetic resonance (MR) spectroscopy and imaging methods have been developed in conjunction with hyperpolarization of nuclear spins. These approaches enable noninvasive monitoring of tumor progression and treatment efficacy and are being tested in multiple clinical trials...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28627365/mitochondria-metabolic-reprogramming-in-the-formation-of-neurons-from-peripheral-cells-cause-or-consequence-and-the-implications-to-their-utility
#13
REVIEW
Gary E Gibson, Ankita Thakkar
The induction of pluripotent stem cells (iPSC) from differentiated cells such as fibroblasts and their subsequent conversion to neural progenitor cells (NPC) and finally to neurons is intriguing scientifically, and its potential to medicine nearly infinite, but unrealized. A better understanding of the changes at each step of the transformation will enable investigators to use them better to model neurological disease. Each step of conversion from a differentiated cell to an iPSC to a NPC to neurons requires large changes in glycolysis including aerobic glycolysis, the pentose shunt, the tricarboxylic acid cycle, the electron transport chain and in the production of reactive oxygen species (ROS)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28621418/single-cell-analysis-of-the-inner-ear-sensory-organs
#14
Ofer Yizhar-Barnea, Karen B Avraham
The inner ear is composed of a complex mixture of cells, which together allow organisms to hear and maintain balance. The cells in the inner ear, which undergo an extraordinary process of development, have only recently begun to be studied on an individual level. As it has recently become clear that individual cells, previously considered to be of uniform character, may differ dramatically from each other, the need to study cell-to-cell variation, along with distinct transcriptional and regulatory signatures, has taken hold in the scientific community...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28620452/metabolic-reprogramming-during-the-trypanosoma-brucei-life-cycle
#15
REVIEW
Terry K Smith, Frédéric Bringaud, Derek P Nolan, Luisa M Figueiredo
Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites...
2017: F1000Research
https://www.readbyqxmd.com/read/28620044/let-there-be-light-how-to-use-photoswitchable-cross-linker-to-reprogram-proteins
#16
REVIEW
Daniel Hoersch
Azobenzene is a photo-isomerizing molecule whose end-to-end distance changes upon external illumination. When combined with site-specific reactive groups, it can be used as molecular tweezers to remote-control the structure and function of protein targets. The present study gives a brief overview over the rational design strategies that use an azobenzene-based photoswitchable cross-linker to engineer ON/OFF switches into functional proteins or to reprogram proteins for novel functions. The re-engineered proteins may be used as remote controls for cellular pathways, as light-gated drug delivery platforms or as light-powered machinery of synthetic cells and micro-scaled factories...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28614042/bnip3l-nix-dependent-mitophagy-regulates-cell-differentiation-via-metabolic-reprogramming
#17
Lorena Esteban-Martínez, Patricia Boya
Macroautophagy/autophagy is the process by which cellular components are degraded and recycled within the lysosome. These components include mitochondria, the selective degradation of which is known as mitophagy. Mitochondria are dynamic organelles that constantly adapt their morphology, function, and number to accommodate the metabolic needs of the cell. Extensive metabolic reconfiguration occurs during cell differentiation, when mitochondrial activity increases in most cell types. However, our data demonstrate that during physiological retinal ganglion cell (RGC) development, mitophagy-dependent metabolic reprogramming towards glycolysis regulates numbers of RGCs, which are the first neurons to differentiate in the retina and whose axons form the optic nerve...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28611673/reversing-egfr-mediated-immunoescape-by-targeted-monoclonal-antibody-therapy
#18
REVIEW
Fernando Concha-Benavente, Robert L Ferris
Uncontrolled growth is a signature of carcinogenesis, in part mediated by overexpression or overstimulation of growth factor receptors. The epidermal growth factor receptor (EGFR) mediates activation of multiple oncogenic signaling pathways and escape from recognition by the host immune system. We discuss how EGFR signaling downregulates tumor antigen presentation, upregulates suppressive checkpoint receptor ligand programmed death ligand (PD-L1), induces secretion of inhibitory molecules such as transforming growth factor beta (TGFβ) and reprograms the metabolic pathways in cancer cells to upregulate aerobic glycolysis and lactate secretion that ultimately lead to impaired cellular immunity mediated by natural killer (NK) cell and cytotoxic T lymphocytes (CTL)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28607562/cellular-reprogramming-genome-editing-and-alternative-crispr-cas9-technologies-for-precise-gene-therapy-of-duchenne-muscular-dystrophy
#19
REVIEW
Peter Gee, Huaigeng Xu, Akitsu Hotta
In the past decade, the development of two innovative technologies, namely, induced pluripotent stem cells (iPSCs) and the CRISPR Cas9 system, has enabled researchers to model diseases derived from patient cells and precisely edit DNA sequences of interest, respectively. In particular, Duchenne muscular dystrophy (DMD) has been an exemplary monogenic disease model for combining these technologies to demonstrate that genome editing can correct genetic mutations in DMD patient-derived iPSCs. DMD is an X-linked genetic disorder caused by mutations that disrupt the open reading frame of the dystrophin gene, which plays a critical role in stabilizing muscle cells during contraction and relaxation...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28602818/cell-cycle-control-by-pten
#20
REVIEW
Andrew Brandmaier, Sheng-Qi Hou, Wen H Shen
Continuous and error-free chromosome inheritance through the cell cycle is essential for genomic stability and tumor suppression. However, accumulation of aberrant genetic materials often causes the cell cycle to go awry, leading to malignant transformation. In response to genotoxic stress, cells employ diverse adaptive mechanisms to halt or exit the cell cycle temporarily or permanently. The intrinsic machinery of cycling, resting, and exiting shapes the cellular response to extrinsic stimuli, whereas prevalent disruption of the cell cycle machinery in tumor cells often confers resistance to anticancer therapy...
June 9, 2017: Journal of Molecular Biology
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