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Cellular reprograming

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https://www.readbyqxmd.com/read/29220654/a-unique-isr-program-determines-cellular-responses-to-chronic-stress
#1
Bo-Jhih Guan, Vincent van Hoef, Raul Jobava, Orna Elroy-Stein, Leos S Valasek, Marie Cargnello, Xing-Huang Gao, Dawid Krokowski, William C Merrick, Scot R Kimball, Anton A Komar, Antonis E Koromilas, Anthony Wynshaw-Boris, Ivan Topisirovic, Ola Larsson, Maria Hatzoglou
The integrated stress response (ISR) is a homeostatic mechanism induced by endoplasmic reticulum (ER) stress. In acute/transient ER stress, decreased global protein synthesis and increased uORF mRNA translation are followed by normalization of protein synthesis. Here, we report a dramatically different response during chronic ER stress. This chronic ISR program is characterized by persistently elevated uORF mRNA translation and concurrent gene expression reprogramming, which permits simultaneous stress sensing and proteostasis...
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29218051/sphingosine-1-phosphate-and-c-c-chemokine-receptor-2-dependent-activation-of-cd4-plasmacytoid-dendritic-cells-in-the-bone-marrow-contributes-to-signs-of-sepsis-induced-immunosuppression
#2
Anna Smirnov, Stephanie Pohlmann, Melanie Nehring, Shafaqat Ali, Ritu Mann-Nüttel, Stefanie Scheu, Anne-Charlotte Antoni, Wiebke Hansen, Manuela Büettner, Miriam J Gardiasch, Astrid M Westendorf, Florian Wirsdörfer, Eva Pastille, Marcel Dudda, Stefanie B Flohé
Sepsis is the dysregulated response of the host to systemic, mostly bacterial infection, and is associated with an enhanced susceptibility to life-threatening opportunistic infections. During polymicrobial sepsis, dendritic cells (DCs) secrete enhanced levels of interleukin (IL) 10 due to an altered differentiation in the bone marrow and contribute to the development of immunosuppression. We investigated the origin of the altered DC differentiation using murine cecal ligation and puncture (CLP), a model for human polymicrobial sepsis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29217772/the-intracellular-immune-receptor-rx1-regulates-the-dna-binding-activity-of-a-golden2-like-transcription-factor
#3
Philip D Townsend, Christopher H Dixon, Erik J Slootweg, Octavina Ca Sukarta, Ally Wh Yang, Timothy R Hughes, Gary J Sharples, Lars-Olof Palsson, Frank L W Takken, Aska Goverse, Martin J Cann
Plant NLR proteins enable the immune system to recognise and respond to pathogen attack. An early consequence of immune activation is transcriptional reprogramming and some NLRs have been shown to act in the nucleus and interact with transcription factors. The Rx1 NLR protein of potato is further able to bind and distort double-stranded DNA. However, Rx1 host targets that support a role for Rx1 in transcriptional reprogramming at DNA are unknown. Here we report a functional interaction between Rx1 and NbGlk1, a Golden2- like transcription factor...
December 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29217199/efficient-generation-of-transgene-and-feeder-free-induced-pluripotent-stem-cells-from-human-dental-mesenchymal-stem-cells-and-their-chemically-defined-differentiation-into-cardiomyocytes
#4
Xiaobing Tan, Qingli Dai, Tao Guo, Jingshu Xu, Qingyuan Dai
Advance in stem cell research resulted in several processes to generate induced pluripotent stem cells (iPSCs) from adult somatic cells. In our previous study, the reprogramming of iPSCs from human dental mesenchymal stem cells (MSCs) including SCAP and DPSCs, has been reported. Herein, safe iPSCs were reprogrammed from SCAP and DPSCs using non-integrating RNA virus vector, which is an RNA virus carrying no risk of altering host genome. DPSCs- and SCAP-derived iPSCs exhibited the characteristics of the classical morphology with human embryonic stem cells (hESCs) without integration of foreign genes, indicating the potential of their clinical application...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29215097/the-molecular-dialogue-between-arabidopsis-thaliana-and-the-necrotrophic-fungus-botrytis-cinerea-leads-to-major-changes-in-host-carbon-metabolism
#5
Florian Veillet, Cécile Gaillard, Pauline Lemonnier, Pierre Coutos-Thévenot, Sylvain La Camera
Photoassimilates play crucial roles during plant-pathogen interactions, as colonizing pathogens rely on the supply of sugars from hosts. The competition for sugar acquisition at the plant-pathogen interface involves different strategies from both partners which are critical for the outcome of the interaction. Here, we dissect individual mechanisms of sugar uptake during the interaction of Arabidopsis thaliana with the necrotrophic fungus Botrytis cinerea using millicell culture insert, that enables molecular communication without physical contact...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212856/tamoxifen-resistance-in-breast-cancer-is-regulated-by-the-ezh2-er%C3%AE-greb1-transcriptional-axis
#6
Yanming Wu, Zhao Zhang, Mauro E Cenciarini, Cecilia J Proietti, Matias F Amasino, Tao Hong, Mei Yang, Yiji Liao, Huai-Chin Chiang, Virginia Kaklamani, Rinath Jeselsohn, Ratna K Vadlamudi, Tim H-M Huang, Rong Li, Carmine De Angelis, Xiaoyong Fu, Patricia V Elizalde, Rachel Schiff, Myles Brown, Kexin Xu
Resistance to cancer treatment can be driven by epigenetic reprogramming of specific transcriptomes in favor of the refractory phenotypes. Here we discover that tamoxifen resistance in breast cancer is driven by a regulatory axis consisting of a master transcription factor, its cofactor and an epigenetic regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen resistance by silencing the expression of the estrogen receptor α (ERα) cofactor GREB1. In clinical specimens, induction of DNA methylation of a particular CpG enriched region at the GREB1 promoter negatively correlated with GREB1 levels and cell sensitivity to endocrine agents...
December 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/29212308/metabolic-signaling-to-epigenetic-alterations-in-cancer
#7
REVIEW
Jung-Ae Kim, Young Il Yeom
Cancer cells reprogram cellular metabolism to support the malignant features of tumors, such as rapid growth and proliferation. The cancer promoting effects of metabolic reprogramming are found in many aspects: generating additional energy, providing more anabolic molecules for biosynthesis, and rebalancing cellular redox states in cancer cells. Metabolic pathways are considered the pipelines to supply metabolic cofactors of epigenetic modifiers. In this regard, cancer metabolism, whereby cellular metabolite levels are greatly altered compared to normal levels, is closely associated with cancer epigenetics, which is implicated in many stages of tumorigenesis...
December 7, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29212260/bioenergetics-of-acquired-cisplatin-resistant-h1299-non-small-cell-lung-cancer-and-p31-mesothelioma-cells
#8
Fintan Geoghegan, Robert J Buckland, Eric T Rogers, Karima Khalifa, Emma B O'Connor, Mary F Rooney, Parviz Behnam-Motlagh, Torbjörn K Nilsson, Kjell Grankvist, Richard K Porter
Acquired cisplatin resistance is a common feature of tumours following cancer treatment with cisplatin and also of non-small cell lung cancer (H1299) and mesothelioma (P31) cell lines exposed to cisplatin. To elucidate the cellular basis of acquired cisplatin resistance, a comprehensive bioenergetic analysis was undertaken. We demonstrate that cellular oxygen consumption was significantly decreased in cisplatin resistant cells and that the reduction was primarily due to reduced mitochondrial activity as a result of reduced mitochondrial abundance...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212199/klf4-reduces-stemness-phenotype-triggers-mesenchymal-epithelial-transition-met-like-molecular-changes-and-prevents-tumor-progression-in-nasopharygeal-carcinoma
#9
Xiqing Li, Zhunlan Zhao, Xiaoling Zhang, Sheng Yang, Xia Lin, Xinglong Yang, Xiaolin Lin, Junwen Shi, Shengchun Wang, Wentao Zhao, Jing Li, Fei Gao, Mingyue Liu, Ning Ma, Weiren Luo, Kaitai Yao, Yan Sun, Shengjun Xiao, Dong Xiao, Junshuang Jia
The reprogramming factor Krüppel-like factor 4 (Klf4), one of the Yamanaka's reprogramming factors, plays an essential role in reprogramming somatic cells into induced pluripotent stem cells (iPSCs). Klf4 is dysregulated and displays divergent functions in multiple malignancies, but the biological roles of Klf4 in nasopharyngeal carcinoma (NPC) remain unknown. The present study revealed that Klf4 downregulation in a cohort of human NPC biopsies is significantly associated with invasive and metastatic phenotypes of NPC...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212182/oncogenic-p95her2-611ctf-primes-human-breast-epithelial-cells-for-metabolic-stress-induced-down-regulation-of-flip-and-activation-of-trail-r-caspase-8-dependent-apoptosis
#10
Rosa Martín-Pérez, Rosario Yerbes, Rocío Mora-Molina, Ana Cano-González, Joaquín Arribas, Massimiliano Mazzone, Abelardo López-Rivas, Carmen Palacios
Oncogenic transformation triggers reprogramming of cell metabolism, as part of the tumorigenic process. However, metabolic reprogramming may also increase the sensitivity of transformed cells to microenvironmental stress, at the early stages of tumor development. Herein, we show that transformation of human breast epithelial cells by the p95HER2/611CTF oncogene markedly sensitizes these cells to metabolic stress induced by the simultaneous inhibition of glucose and glutamine metabolism. In p95HER2/611CTF-transformed cells, metabolic stress activates a TNF related apoptosis-inducing ligand (TRAIL)-R and caspase-8-dependent apoptotic process that requires prior down-regulation of cellular FLICE-like inhibitor protein (c-FLIP) levels...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211687/cellular-reprogramming-dynamics-follow-a-simple-1d-reaction-coordinate
#11
Sai Teja Pusuluri, Alex H Lang, Pankaj Mehta, Horacio E Castillo
Cellular reprogramming, the conversion of one cell type to another, induces global changes in gene expression involving thousands of genes, and understanding how cells globally alter their gene expression profile during reprogramming is an ongoing problem. Here we reanalyze time-course data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple 1D reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of the experimental protocol used...
December 6, 2017: Physical Biology
https://www.readbyqxmd.com/read/29210177/mitochondrial-fission-promotes-cell-migration-by-ca2-camkii-erk-fak-pathway-in-hepatocellular-carcinoma
#12
Xiacheng Sun, Haiyan Cao, Lei Zhan, Chun Yin, Gang Wang, Ping Liang, Jibin Li, Zhe Wang, Bingrong Liu, Qichao Huang, Jinliang Xing
BACKGROUND AND AIMS: Mitochondrial dynamics of fission and fusion plays critical roles in a diverse range of important cellular functions, and its deregulation has been increasingly implicated in human diseases. Previous studies have shown that increased mitochondrial fission significantly promoted the proliferation of hepatocellular carcinoma (HCC) cells. However, how they influence the migration of tumor cells remained largely unknown. METHODS: In the present study, we further investigated the effect of mitochondrial fission on the migration and metastasis of HCC cells...
December 6, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29208682/the-receptor-tyrosine-kinase-epha2-promotes-glutamine-metabolism-in-tumors-by-activating-the-transcriptional-coactivators-yap-and-taz
#13
Deanna N Edwards, Verra M Ngwa, Shan Wang, Eileen Shiuan, Dana M Brantley-Sieders, Laura C Kim, Albert B Reynolds, Jin Chen
Malignant tumors reprogram cellular metabolism to support cancer cell proliferation and survival. Although most cancers depend on a high rate of aerobic glycolysis, many cancer cells also display addiction to glutamine. Glutamine transporters and glutaminase activity are critical for glutamine metabolism in tumor cells. We found that the receptor tyrosine kinase EphA2 activated the TEAD family transcriptional coactivators YAP and TAZ (YAP/TAZ), likely in a ligand-independent manner, to promote glutamine metabolism in cells and mouse models of HER2-positive breast cancer...
December 5, 2017: Science Signaling
https://www.readbyqxmd.com/read/29206173/histone-macroh2a1-a-chromatin-point-of-intersection-between-fasting-senescence-and-cellular-regeneration
#14
REVIEW
Oriana Lo Re, Manlio Vinciguerra
Histone variants confer chromatin unique properties. They have specific genomic distribution, regulated by specific deposition and removal machineries. Histone variants, mostly of canonical histones H2A, H2B and H3, have important roles in early embryonic development, in lineage commitment of stem cells, in the converse process of somatic cell reprogramming to pluripotency and, in some cases, in the modulation of animal aging and life span. MacroH2A1 is a variant of histone H2A, present in two alternatively exon-spliced isoforms macroH2A1...
December 5, 2017: Genes
https://www.readbyqxmd.com/read/29204835/oral-cancer-stem-cells-microenvironment
#15
Prajna Paramita Naik, Prashanta Kumar Panda, Sujit K Bhutia
Cancer stem cells (CSCs) play important role in tumor growth and metastasis coupled with increased recurrences and acquired therapeutic resistance in oral cancer. The tumor microenvironment imposes intense pressure in cancer evolution in response to adverse growth conditions, resource limitation and immune predation. Here, we discussed the dynamic interplay between cancer stem cells and tumor microenvironment in the formation of intratumoral heterogeneity to modulate tumor progression. The CSCs niche provide a special microhabitat for survival, maintenance of stemness and tumor re-propagation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29203658/molecular-and-functional-resemblance-of-differentiated-cells-derived-from-isogenic-human-ipscs-and-scnt-derived-escs
#16
Ming-Tao Zhao, Haodong Chen, Qing Liu, Ning-Yi Shao, Nazish Sayed, Hung-Ta Wo, Joe Z Zhang, Sang-Ging Ong, Chun Liu, Youngkyun Kim, Huaxiao Yang, Tony Chour, Hong Ma, Nuria Marti Gutierrez, Ioannis Karakikes, Shoukhrat Mitalipov, Michael P Snyder, Joseph C Wu
Patient-specific pluripotent stem cells (PSCs) can be generated via nuclear reprogramming by transcription factors (i.e., induced pluripotent stem cells, iPSCs) or by somatic cell nuclear transfer (SCNT). However, abnormalities and preclinical application of differentiated cells generated by different reprogramming mechanisms have yet to be evaluated. Here we investigated the molecular and functional features, and drug response of cardiomyocytes (PSC-CMs) and endothelial cells (PSC-ECs) derived from genetically relevant sets of human iPSCs, SCNT-derived embryonic stem cells (nt-ESCs), as well as in vitro fertilization embryo-derived ESCs (IVF-ESCs)...
December 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29203613/nfe2l1-silenced-insulinoma-cells-acquire-aggressiveness-and-chemo-resistance
#17
Jingqi Fu, Hongzhi Zheng, Qi Cui, Chengjie Chen, Simeng Bao, Jing Sun, Lu Li, Bei Yang, Huihui Wang, Yongyong Hou, Yuanyuan Xu, Yuanhong Xu, Qiang Zhang, Jingbo Pi
The transcription factor nuclear factor erythroid 2 like 1 (NFE2L1 or NRF1) is involved in various critical cell processes such as maintenance of ubiquitin-proteasome system and regulation of the cellular antioxidant response. We previously determined that pancreatic β-cell-specific Nfe2l1-knockout mice had hyperinsulinemia, and that silencing of Nfe2l1 in mouse islets or MIN6 insulinoma β-cells induced elevated basal insulin release and altered glucose metabolism. Hypoglycemia is a major issue with aggressive insulinomas, although a role of NFE2L1 in this pathology is not defined...
December 4, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29202474/adhfe1-is-a-breast-cancer-oncogene-and-induces-metabolic-reprogramming
#18
Prachi Mishra, Wei Tang, Vasanta Putluri, Tiffany H Dorsey, Feng Jin, Fang Wang, Donewei Zhu, Lauren Amable, Tao Deng, Shaofei Zhang, J Keith Killian, Yonghong Wang, Tsion Z Minas, Harry G Yfantis, Dong H Lee, Arun Sreekumar, Michael Bustin, Wei Liu, Nagireddy Putluri, Stefan Ambs
Metabolic reprogramming in breast tumors is linked to increases in putative oncogenic metabolites that may contribute to malignant transformation. We previously showed that accumulation of the oncometabolite, 2-hydroxyglutarate (2HG), in breast tumors was associated with MYC signaling, but not with isocitrate dehydrogenase (IDH) mutations, suggesting a distinct mechanism for increased 2HG in breast cancer. Here, we determined that D-2HG is the predominant enantiomer in human breast tumors and show that the D-2HG-producing mitochondrial enzyme, alcohol dehydrogenase, iron-containing protein 1 (ADHFE1), is a breast cancer oncogene that decreases patient survival...
November 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29198150/the-effect-of-tumor-derived-exosomes-on-immune-regulation-and-cancer-immunotherapy
#19
Theresa L Whiteside
Tumor-derived exosomes (TEX) carry both immunosuppressive and immunostimulatory receptor/ligands that in part mimic the profiles of the parent tumor cells. Operating as an intercellular communication system, TEX deliver protumor or antitumor signals to immune and nonimmune cells reprogramming their functions. Mechanisms responsible for cellular reprogramming include cell surface signaling and/or uptake of TEX by recipient cells. Once internalized, TEX transfer mRNA, miRNA and proteins that promote transcriptional/translational activities...
December 2017: Future Oncology
https://www.readbyqxmd.com/read/29197748/emergence-of-synthetic-mrna-in%C3%A2-vitro-synthesis-of-mrna-and-its-applications-in-regenerative-medicine
#20
REVIEW
Hyokyoung Kwon, Minjeong Kim, Yunmi Seo, Yae Seul Moon, Hwa Jeong Lee, Kyuri Lee, Hyukjin Lee
The field of gene therapy has evolved over the past two decades after the first introduction of nucleic acid drugs, such as plasmid DNA (pDNA). With the development of in vitro transcription (IVT) methods, synthetic mRNA has become an emerging class of gene therapy. IVT mRNA has several advantages over conventional pDNA for the expression of target proteins. mRNA does not require nuclear localization to mediate protein translation. The intracellular process for protein expression is much simpler and there is no potential risk of insertion mutagenesis...
November 23, 2017: Biomaterials
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