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Direct Reprogramming

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https://www.readbyqxmd.com/read/28749470/mir-181d-and-c-myc-mediated-inhibition-of-cry2-and-fbxl3-reprograms-metabolism-in-colorectal-cancer
#1
Xiaofeng Guo, Yuekun Zhu, Xinya Hong, Mukun Zhang, Xingfeng Qiu, Zhenfa Wang, Zhongquan Qi, Xuehui Hong
Colorectal cancer (CRC) is the second major cause of tumor-related deaths. MicroRNAs (miRNAs) have pivotal roles in CRC progression. Here, we describe the effect of miR-181d on CRC cell metabolism and underlying molecular mechanism. Our data firmly demonstrated that knockdown of miR-181d suppressed CRC cell proliferation, migration, and invasion by impairing glycolysis. Mechanistically, miR-181d stabilized c-myc through directly targeting the 3'-UTRs of CRY2 and FBXL3, which subsequently increased the glucose consumption and the lactate production...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28737766/endothelial-fibrosis-induced-by-suppressed-stat3-expression-mediated-by-signaling-involving-the-tgf-%C3%AE-1-alk5-smad-pathway
#2
Alvaro Becerra, Macarena Rojas, Alejandro Vallejos, Vicente Villegas, Lorena Pérez, Claudio Cabello-Verrugio, Felipe Simon
During systemic inflammatory pathologies, mediators of inflammation circulate in the bloodstream and interact with endothelial cells (ECs), resulting in endothelial dysfunction that maintains and enhances the pathological condition. Inflammatory mediators change the protein expression profile of ECs, which become activated fibroblasts via endothelial-to-mesenchymal transition. This process is characterized by downregulated endothelial proteins and strongly upregulated fibrotic-specific genes and extracellular matrix-forming proteins...
July 24, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28737745/electromagnetized-gold-nanoparticles-mediate-direct-lineage-reprogramming-into-induced-dopamine-neurons-in-vivo-for-parkinson-s-disease-therapy
#3
Junsang Yoo, Euiyeon Lee, Hee Young Kim, Dong-Ho Youn, Junghyun Jung, Hongwon Kim, Yujung Chang, Wonwoong Lee, Jaein Shin, Soonbong Baek, Wonhee Jang, Won Jun, Soochan Kim, Jongki Hong, Hi-Joon Park, Christopher J Lengner, Sang Hyun Moh, Youngeun Kwon, Jongpil Kim
Electromagnetic fields (EMF) are physical energy fields generated by electrically charged objects, and specific ranges of EMF can influence numerous biological processes, which include the control of cell fate and plasticity. In this study, we show that electromagnetized gold nanoparticles (AuNPs) in the presence of specific EMF conditions facilitate an efficient direct lineage reprogramming to induced dopamine neurons in vitro and in vivo. Remarkably, electromagnetic stimulation leads to a specific activation of the histone acetyltransferase Brd2, which results in histone H3K27 acetylation and a robust activation of neuron-specific genes...
July 17, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28736567/dynamics-of-calcium-during-in-vitro-microspore-embryogenesis-and-in-vivo-microspore-development-in-brassica-napus-and-solanum-melongena
#4
Alba Rivas-Sendra, Antonio Calabuig-Serna, Jose M Seguí-Simarro
Calcium is widely known to have a role as a signaling molecule in many different processes, including stress response and activation of the embryogenic program. However, there are no direct clues about calcium levels during microspore embryogenesis, an experimental process that combines a developmental switch toward embryogenesis and the simultaneous application of different stressing factors. In this work, we used FluoForte, a calcium-specific fluorescent vital dye, to track by confocal microscopy the changes in levels and subcellular distribution of calcium in living rapeseed (B...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28733419/myc2-orchestrates-a-hierarchical-transcriptional-cascade-that-regulates-jasmonate-mediated-plant-immunity-in-tomato
#5
Minmin Du, Jiuhai Zhao, David T W Tzeng, Yuanyuan Liu, Lei Deng, Tianxia Yang, Qingzhe Zhai, Fangming Wu, Zhuo Huang, Ming Zhou, Qiaomei Wang, Qian Chen, Silin Zhong, Chang-Bao Li, Chuanyou Li
The hormone jasmonate (JA), which functions in plant immunity, regulates resistance to pathogen infection and insect attack through triggering genome-wide transcriptional reprogramming in plants. We show that the basic helix-loop-helix transcription factor (TF) MYC2 in tomato (Solanum lycopersicum) acts downstream of the JA receptor to orchestrate JA-mediated activation of both the wounding and pathogen responses. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq) assays, we identified 655 MYC2-targeted JA-responsive genes...
July 21, 2017: Plant Cell
https://www.readbyqxmd.com/read/28732077/mutations-in-the-caenorhabditis-elegans-orthologs-of-human-genes-required-for-mitochondrial-trna-modification-cause-similar-electron-transport-chain-defects-but-different-nuclear-responses
#6
Carmen Navarro-González, Ismaïl Moukadiri, Magda Villarroya, Ernesto López-Pascual, Simon Tuck, M-Eugenia Armengod
Several oxidative phosphorylation (OXPHOS) diseases are caused by defects in the post-transcriptional modification of mitochondrial tRNAs (mt-tRNAs). Mutations in MTO1 or GTPBP3 impair the modification of the wobble uridine at position 5 of the pyrimidine ring and cause heart failure. Mutations in TRMU affect modification at position 2 and cause liver disease. Presently, the molecular basis of the diseases and why mutations in the different genes lead to such different clinical symptoms is poorly understood...
July 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28725231/chloroplast-redox-status-modulates-genome-wide-plant-responses-during-the-non-host-interaction-of-tobacco-with-the-hemibiotrophic-bacterium-xanthomonas-campestris-pv-vesicatoria
#7
Juan J Pierella Karlusich, Matias D Zurbriggen, Fahimeh Shahinnia, Sophia Sonnewald, Uwe Sonnewald, Seyed A Hosseini, Mohammad-Reza Hajirezaei, Néstor Carrillo
Non-host resistance is the most ample and durable form of plant resistance against pathogen infection. It includes induction of defense-associated genes, massive metabolic reprogramming, and in many instances, a form of localized cell death (LCD) at the site of infection, purportedly designed to limit the spread of biotrophic and hemibiotrophic microorganisms. Reactive oxygen species (ROS) have been proposed to act as signals for LCD orchestration. They are produced in various cellular compartments including chloroplasts, mitochondria and apoplast...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28724614/nuclear-mtor-acts-as-a-transcriptional-integrator-of-the-androgen-signaling-pathway-in-prostate-cancer
#8
Étienne Audet-Walsh, Catherine R Dufour, Tracey Yee, Fatima Z Zouanat, Ming Yan, Georges Kalloghlian, Mathieu Vernier, Maxime Caron, Guillaume Bourque, Eleonora Scarlata, Lucie Hamel, Fadi Brimo, Armen G Aprikian, Jacques Lapointe, Simone Chevalier, Vincent Giguère
Androgen receptor (AR) signaling reprograms cellular metabolism to support prostate cancer (PCa) growth and survival. Another key regulator of cellular metabolism is mTOR, a kinase found in diverse protein complexes and cellular localizations, including the nucleus. However, whether nuclear mTOR plays a role in PCa progression and participates in direct transcriptional cross-talk with the AR is unknown. Here, via the intersection of gene expression, genomic, and metabolic studies, we reveal the existence of a nuclear mTOR-AR transcriptional axis integral to the metabolic rewiring of PCa cells...
July 19, 2017: Genes & Development
https://www.readbyqxmd.com/read/28716939/distinct-requirements-for-energy-metabolism-in-mouse-primordial-germ-cells-and-their-reprogramming-to-embryonic-germ-cells
#9
Yohei Hayashi, Kei Otsuka, Masayuki Ebina, Kaori Igarashi, Asuka Takehara, Mitsuyo Matsumoto, Akio Kanai, Kazuhiko Igarashi, Tomoyoshi Soga, Yasuhisa Matsui
Primordial germ cells (PGCs), undifferentiated embryonic germ cells, are the only cells that have the ability to become gametes and to reacquire totipotency upon fertilization. It is generally understood that the development of PGCs proceeds through the expression of germ cell-specific transcription factors and characteristic epigenomic changes. However, little is known about the properties of PGCs at the metabolite and protein levels, which are directly responsible for the control of cell function. Here, we report the distinct energy metabolism of PGCs compared with that of embryonic stem cells...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28713772/harnessing-neutrophil-survival-mechanisms-during-chronic-infection-by-pseudomonas-aeruginosa-novel-therapeutic-targets-to-dampen-inflammation-in-cystic-fibrosis
#10
REVIEW
Benoît S Marteyn, Pierre-Régis Burgel, Laurent Meijer, Véronique Witko-Sarsat
More than two decades after cloning the cystic fibrosis transmembrane regulator (CFTR) gene, the defective gene in cystic fibrosis (CF), we still do not understand how dysfunction of this ion channel causes lung disease and the tremendous neutrophil burden which persists within the airways; nor why chronic colonization by Pseudomonas aeruginosa develops in CF patients who are thought to be immunocompetent. It appears that the microenvironment within the lung of CF patients provides favorable conditions for both P...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28712493/crispr-cas9-enabled-multiplex-genome-editing-and-its-application
#11
Bastian Minkenberg, Matthew Wheatley, Yinong Yang
The CRISPR/Cas9 system is a prevalent and versatile genome-editing tool of choice for basic and applied biological research. An exchange of a 20-bp spacer sequence in the gRNA can easily reprogram Cas9 to target a different DNA site. By expressing or providing multiple gRNAs, the system also enables multiplex genome editing at high efficiencies. Current approaches for providing multiple gRNAs in vivo include the use of multigene cassettes to express several gRNAs, Csy4-based excision, arrays of crRNAs, ribozyme-flanked gRNAs, tRNA-dependent cleavage of gRNAs, and direct introduction of Cas9 proteins preloaded with different gRNAs...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28711329/cardiac-reprogramming-factor-gata4-reduces-postinfarct-cardiac-fibrosis-through-direct-repression-of-the-profibrotic-mediator-snail
#12
Megumi Mathison, Vivek P Singh, Deepthi Sanagasetti, Lina Yang, Jaya Pratap Pinnamaneni, Jianchang Yang, Todd K Rosengart
OBJECTIVE: The administration of a variety of reprogramming factor cocktails has now been shown to reprogram cardiac fibroblasts into induced cardiomyocyte-like cells. However, reductions in ventricular fibrosis observed after reprogramming factor administration seem to far exceed the extent of induced cardiomyocyte-like cell generation in vivo. We investigated whether reprogramming factor administration might primarily play a role in activating antifibrotic molecular pathways. METHODS: Adult rat cardiac fibroblasts were infected with lentivirus encoding the transcription factors Gata4, Mef2c, or Tbx5, all 3 vectors, or a green fluorescent protein control vector...
June 21, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28711155/manufacturing-cell-therapies-using-engineered-biomaterials
#13
REVIEW
Amr A Abdeen, Krishanu Saha
Emerging manufacturing processes to generate regenerative advanced therapies can involve extensive genomic and/or epigenomic manipulation of autologous or allogeneic cells. These cell engineering processes need to be carefully controlled and standardized to maximize safety and efficacy in clinical trials. Engineered biomaterials with smart and tunable properties offer an intriguing tool to provide or deliver cues to retain stemness, direct differentiation, promote reprogramming, manipulate the genome, or select functional phenotypes...
July 12, 2017: Trends in Biotechnology
https://www.readbyqxmd.com/read/28708602/development-of-hepatoma-derived-bidirectional-oval-like-cells-as-a-model-to-study-host-interactions-with-hepatitis-c-virus-during-differentiation
#14
Masahiko Ito, Suofeng Sun, Takasuke Fukuhara, Ryosuke Suzuki, Miho Tamai, Toyohiko Yamauchi, Kenji Nakashima, Yoh-Ichi Tagawa, Shigetoshi Okazaki, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki
Directed differentiation of human stem cells including induced pluripotent stem cells into hepatic cells potentially leads to acquired susceptibility to hepatitis C virus (HCV) infection. However, cellular determinants that change their expression during cell reprogramming or hepatic differentiation and are pivotal for supporting the HCV life cycle remain unclear. In this study, by introducing a set of reprogramming factors, we established HuH-7-derived oval-like cell lines, Hdo-17 and -23, which possess features of bipotential liver precursors...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706248/acoustic-transfection-for-genomic-manipulation-of-single-cells-using-high-frequency-ultrasound
#15
Sangpil Yoon, Pengzhi Wang, Qin Peng, Yingxiao Wang, K Kirk Shung
Efficient intracellular delivery of biologically active macromolecules has been a challenging but important process for manipulating live cells for research and therapeutic purposes. There have been limited transfection techniques that can deliver multiple types of active molecules simultaneously into single-cells as well as different types of molecules into physically connected individual neighboring cells separately with high precision and low cytotoxicity. Here, a high frequency ultrasound-based remote intracellular delivery technique capable of delivery of multiple DNA plasmids, messenger RNAs, and recombinant proteins is developed to allow high spatiotemporal visualization and analysis of gene and protein expressions as well as single-cell gene editing using clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease (Cas9), a method called acoustic-transfection...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697461/direct-induction-of-functional-neuronal-cells-from-fibroblast-like-cells-derived-from-adult-human-retina
#16
Lili Hao, Zhen Xu, Hui Sun, Wu Luo, Youchen Yan, Jing Wang, Jingyi Guo, Yizhi Liu, Shuyi Chen
Obtaining and manipulating neuronal cells are critical for neural biology basic mechanism studies and translational applications. Recent advances in protocol development and mechanism dissections have made direct induction of neuronal cells from other somatic cells (iN) a promising strategy for such purposes. In this study, we established a protocol to expand a population of fibroblast-like cells from adult human retinal tissues, which can be reprogrammed into iNs by forced expression of neurogenic transcription factors...
June 29, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28694812/induction-of-innate-immune-memory-by-engineered-nanoparticles-a-hypothesis-that-may-become-true
#17
Paola Italiani, Diana Boraschi
Innate immune memory is the capacity of cells of the innate immune system, such as monocytes and macrophages, to react differently to an inflammatory or infectious challenge if previously exposed to the same or to another agent. Innate immune memory is a protective mechanism, based on epigenetic reprogramming, that ensures effective protection while limiting side effects of tissue damage, by controlling innate/inflammatory responses to repeated stimulations. Engineered nanoparticles (NPs) are novel challenges for our innate immune system, and their ability to induce inflammatory activation, thereby posing health risks, is currently being investigated with controversial results...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28691660/endoribonuclease-type-ii-toxin-antitoxin-systems-functional-or-selfish
#18
Bhaskar Chandra Mohan Ramisetty, Ramachandran Sarojini Santhosh
Most bacterial genomes have multiple type II toxin-antitoxin systems (TAs) that encode two proteins which are referred to as a toxin and an antitoxin. Toxins inhibit a cellular process, while the interaction of the antitoxin with the toxin attenuates the toxin's activity. Endoribonuclease-encoding TAs cleave RNA in a sequence-dependent fashion, resulting in translational inhibition. To account for their prevalence and retention by bacterial genomes, TAs are credited with clinically significant phenomena, such as bacterial programmed cell death, persistence, biofilms and anti-addiction to plasmids...
July 8, 2017: Microbiology
https://www.readbyqxmd.com/read/28690140/new-neurons-in-adult-brain-distribution-molecular-mechanisms-and-therapies
#19
REVIEW
Annachiara Pino, Guido Fumagalli, Francesco Bifari, Ilaria Decimo
"Are new neurons added in the adult mammalian brain?" "Do neural stem cells activate following CNS diseases?" "How can we modulate their activation to promote recovery?" Recent findings in the field provide novel insights for addressing these questions from a new perspective. In this review, we will summarize the current knowledge about adult neurogenesis and neural stem cell niches in healthy and pathological conditions. We will first overview the milestones that have led to the discovery of the classical ventricular and hippocampal neural stem cell niches...
July 8, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28689382/-potential-application-for-stem-cells-in-regenerative-medicine-and-transplantology
#20
Aleksandra Szustka, Małgorzata Rogalińska
There are some cells in human body which have an ability to self-renewal and differentiation into particular type of cell. They are classified according to the source of gain and ability to differentiate. Several studies carry on directed stem cells programming toward formation of particular type of cells and also reprogramming somatic stem cells for induced pluripotent stem cells. In the future it could bring hope in elaboration of new ways of disease curing that will give a chance for getting healthy (especially cancers)...
2017: Postepy Biochemii
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