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Cell Reports

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https://www.readbyqxmd.com/read/28813683/tet2-regulates-mast-cell-differentiation-and-proliferation-through-catalytic-and-non-catalytic-activities
#1
Sara Montagner, Cristina Leoni, Stefan Emming, Giulia Della Chiara, Chiara Balestrieri, Iros Barozzi, Viviana Piccolo, Susan Togher, Myunggon Ko, Anjana Rao, Gioacchino Natoli, Silvia Monticelli
No abstract text is available yet for this article.
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813682/circadian-and-feeding-rhythms-orchestrate-the-diurnal-liver-acetylome
#2
Daniel Mauvoisin, Florian Atger, Loïc Dayon, Antonio Núñez Galindo, Jingkui Wang, Eva Martin, Laetitia Da Silva, Ivan Montoliu, Sebastiano Collino, Francois-Pierre Martin, Joanna Ratajczak, Carles Cantó, Martin Kussmann, Felix Naef, Frédéric Gachon
Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813681/uncoupling-the-mitogenic-and-metabolic-functions-of-fgf1-by-tuning-fgf1-fgf-receptor-dimer-stability
#3
Zhifeng Huang, Yi Tan, Junlian Gu, Yang Liu, Lintao Song, Jianlou Niu, Longwei Zhao, Lakshmi Srinivasan, Qian Lin, Jingjing Deng, Yang Li, Daniel J Conklin, Thomas A Neubert, Lu Cai, Xiaokun Li, Moosa Mohammadi
The recent discovery of metabolic roles for fibroblast growth factor 1 (FGF1) in glucose homeostasis has expanded the functions of this classically known mitogen. To dissect the molecular basis for this functional pleiotropy, we engineered an FGF1 partial agonist carrying triple mutations (FGF1(ΔHBS)) that diminished its ability to induce heparan sulfate (HS)-assisted FGF receptor (FGFR) dimerization and activation. FGF1(ΔHBS) exhibited a severely reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1 in vitro and in vivo...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813680/antibiotics-disrupt-coordination-between-transcriptional-and-phenotypic-stress-responses-in-pathogenic-bacteria
#4
Paul A Jensen, Zeyu Zhu, Tim van Opijnen
Bacterial genes that change in expression upon environmental disturbance have commonly been seen as those that must also phenotypically matter. However, several studies suggest that differentially expressed genes are rarely phenotypically important. We demonstrate, for Gram-positive and Gram-negative bacteria, that these seemingly uncoordinated gene sets are involved in responses that can be linked through topological network analysis. However, the level of coordination is stress dependent. While a well-coordinated response is triggered in response to nutrient stress, antibiotics trigger an uncoordinated response in which transcriptionally and phenotypically important genes are neither linked spatially nor in their magnitude...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813679/the-tumor-suppressor-p53-limits-ferroptosis-by-blocking-dpp4-activity
#5
Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R Billiar, Michael T Lotze, Herbert J Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813678/therapeutic-antibodies-to-ganglioside-gd2-evolved-from-highly-selective-germline-antibodies
#6
Eric Sterner, Megan L Peach, Marc C Nicklaus, Jeffrey C Gildersleeve
Antibodies play a crucial role in host defense and are indispensable research tools, diagnostics, and therapeutics. Antibody generation involves binding of genomically encoded germline antibodies followed by somatic hypermutation and in vivo selection to obtain antibodies with high affinity and selectivity. Understanding this process is critical for developing monoclonal antibodies, designing effective vaccines, and understanding autoantibody formation. Prior studies have found that antibodies to haptens, peptides, and proteins evolve from polyspecific germline antibodies...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813677/the-il-17f-il-17rc-axis-promotes-respiratory-allergy-in-the-proximal-airways
#7
Antonella De Luca, Marilena Pariano, Barbara Cellini, Claudio Costantini, Valeria Rachela Villella, Shyam Sushama Jose, Melissa Palmieri, Monica Borghi, Claudia Galosi, Giuseppe Paolicelli, Luigi Maiuri, Jan Fric, Teresa Zelante
The interleukin 17 (IL-17) cytokine and receptor family is central to antimicrobial resistance and inflammation in the lung. Mice lacking IL-17A, IL-17F, or the IL-17RA subunit were compared with wild-type mice for susceptibility to airway inflammation in models of infection and allergy. Signaling through IL-17RA was required for efficient microbial clearance and prevention of allergy; in the absence of IL-17RA, signaling through IL-17RC on epithelial cells, predominantly by IL-17F, significantly exacerbated lower airway Aspergillus or Pseudomonas infection and allergic airway inflammation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#8
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813675/cd44-interacts-with-hif-2%C3%AE-to-modulate-the-hypoxic-phenotype-of-perinecrotic-and-perivascular-glioma-cells
#9
Elinn Johansson, Elisa S Grassi, Vasiliki Pantazopoulou, Bei Tong, David Lindgren, Tracy J Berg, Elin J Pietras, Håkan Axelson, Alexander Pietras
Hypoxia-inducible factors enhance glioma stemness, and glioma stem cells have an amplified hypoxic response despite residing within a perivascular niche. Still, little is known about differential HIF regulation in stem versus bulk glioma cells. We show that the intracellular domain of stem cell marker CD44 (CD44ICD) is released at hypoxia, binds HIF-2α (but not HIF-1α), enhances HIF target gene activation, and is required for hypoxia-induced stemness in glioma. In a glioma mouse model, CD44 was restricted to hypoxic and perivascular tumor regions, and in human glioma, a hypoxia signature correlated with CD44...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813674/an-integrated-systems-biology-approach-identifies-trim25-as-a-key-determinant-of-breast-cancer-metastasis
#10
Logan A Walsh, Mariano J Alvarez, Erich Y Sabio, Marsha Reyngold, Vladimir Makarov, Suranjit Mukherjee, Ken-Wing Lee, Alexis Desrichard, Şevin Turcan, Martin G Dalin, Vinagolu K Rajasekhar, Shuibing Chen, Linda T Vahdat, Andrea Califano, Timothy A Chan
At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813673/multipotent-basal-stem-cells-maintained-in-localized-proximal-niches-support-directed-long-ranging-epithelial-flows-in-human-prostates
#11
Mohammad Moad, Edouard Hannezo, Simon J Buczacki, Laura Wilson, Amira El-Sherif, David Sims, Robert Pickard, Nicholas A Wright, Stuart C Williamson, Doug M Turnbull, Robert W Taylor, Laura Greaves, Craig N Robson, Benjamin D Simons, Rakesh Heer
Sporadic mitochondrial DNA mutations serve as clonal marks providing access to the identity and lineage potential of stem cells within human tissues. By combining quantitative clonal mapping with 3D reconstruction of adult human prostates, we show that multipotent basal stem cells, confined to discrete niches in juxta-urethral ducts, generate bipotent basal progenitors in directed epithelial migration streams. Basal progenitors are then dispersed throughout the entire glandular network, dividing and differentiating to replenish the loss of apoptotic luminal cells...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813672/chromatin-and-transcriptional-analysis-of-mesoderm-progenitor-cells-identifies-hopx-as-a-regulator-of-primitive-hematopoiesis
#12
Nathan J Palpant, Yuliang Wang, Brandon Hadland, Rebecca J Zaunbrecher, Meredith Redd, Daniel Jones, Lil Pabon, Rajan Jain, Jonathan Epstein, Walter L Ruzzo, Ying Zheng, Irwin Bernstein, Adam Margolin, Charles E Murry
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR(+)/CD34(+) endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified candidate regulators of mesodermal lineage determination. HOPX, a non-DNA-binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813671/oct4-and-sox2-work-as-transcriptional-activators-in-reprogramming-human-fibroblasts
#13
Santosh Narayan, Gene Bryant, Shivangi Shah, Georgina Berrozpe, Mark Ptashne
SOX2 and OCT4, in conjunction with KLF4 and cMYC, are sufficient to reprogram human fibroblasts to induced pluripotent stem cells (iPSCs), but it is unclear if they function as transcriptional activators or as repressors. We now show that, like OCT4, SOX2 functions as a transcriptional activator. We substituted SOX2-VP16 (a strong activator) for wild-type (WT) SOX2, and we saw an increase in the efficiency and rate of reprogramming, whereas the SOX2-HP1 fusion (a strong repressor) eliminated reprogramming...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813670/nkx2-1-is-required-in-the-embryonic-septum-for-cholinergic-system-development-learning-and-memory
#14
Lorenza Magno, Caswell Barry, Christoph Schmidt-Hieber, Polyvios Theodotou, Michael Häusser, Nicoletta Kessaris
The transcription factor NKX2-1 is best known for its role in the specification of subsets of cortical, striatal, and pallidal neurons. We demonstrate through genetic fate mapping and intersectional focal septal deletion that NKX2-1 is selectively required in the embryonic septal neuroepithelium for the development of cholinergic septohippocampal projection neurons and large subsets of basal forebrain cholinergic neurons. In the absence of NKX2-1, these neurons fail to develop, causing alterations in hippocampal theta rhythms and severe deficiencies in learning and memory...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813669/the-phage-nucleus-and-tubulin-spindle-are-conserved-among-large-pseudomonas-phages
#15
Vorrapon Chaikeeratisak, Katrina Nguyen, MacKennon E Egan, Marcella L Erb, Anastasia Vavilina, Joe Pogliano
We recently demonstrated that the large Pseudomonas chlororaphis bacteriophage 201φ2-1 assembles a nucleus-like structure that encloses phage DNA and segregates proteins according to function, with DNA processing proteins inside and metabolic enzymes and ribosomes outside the nucleus. Here, we investigate the replication pathway of the Pseudomonas aeruginosa bacteriophages φKZ and φPA3. Bacteriophages φKZ and φPA3 encode a proteinaceous shell that assembles a nucleus-like structure that compartmentalizes proteins and DNA during viral infection...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813668/subnuclear-relocalization-of-structure-specific-endonucleases-in-response-to-dna-damage
#16
Irene Saugar, Alberto Jiménez-Martín, José Antonio Tercero
Structure-specific endonucleases contribute to the maintenance of genome integrity by cleaving DNA intermediates that need to be resolved for faithful DNA repair, replication, or recombination. Despite advances in the understanding of their function and regulation, it is less clear how these proteins respond to genotoxic stress. Here, we show that the structure-specific endonuclease Mus81-Mms4/EME1 relocalizes to subnuclear foci following DNA damage and colocalizes with the endonucleases Rad1-Rad10 (XPF-ERCC1) and Slx1-Slx4...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813667/human-gw182-paralogs-are-the-central-organizers-for-rna-mediated-control-of-transcription
#17
Jessica A Hicks, Liande Li, Masayuki Matsui, Yongjun Chu, Oleg Volkov, Krystal C Johnson, David R Corey
In the cytoplasm, small RNAs can control mammalian translation by regulating the stability of mRNA. In the nucleus, small RNAs can also control transcription and splicing. The mechanisms for RNA-mediated nuclear regulation are not understood and remain controversial, hindering the effective application of nuclear RNAi and investigation of its natural regulatory roles. Here, we reveal that the human GW182 paralogs TNRC6A/B/C are central organizing factors critical to RNA-mediated transcriptional activation. Mass spectrometry of purified nuclear lysates followed by experimental validation demonstrates that TNRC6A interacts with proteins involved in protein degradation, RNAi, the CCR4-NOT complex, the mediator complex, and histone-modifying complexes...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813666/microrna-9-couples-brain-neurogenesis-and-angiogenesis
#18
Romain Madelaine, Steven A Sloan, Nina Huber, James H Notwell, Louis C Leung, Gemini Skariah, Caroline Halluin, Sergiu P Paşca, Gill Bejerano, Mark A Krasnow, Ben A Barres, Philippe Mourrain
In the developing brain, neurons expressing VEGF-A and blood vessels grow in close apposition, but many of the molecular pathways regulating neuronal VEGF-A and neurovascular system development remain to be deciphered. Here, we show that miR-9 links neurogenesis and angiogenesis through the formation of neurons expressing VEGF-A. We found that miR-9 directly targets the transcription factors TLX and ONECUTs to regulate VEGF-A expression. miR-9 inhibition leads to increased TLX and ONECUT expression, resulting in VEGF-A overexpression...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813665/lineage-restricted-mammary-stem-cells-sustain-the-development-homeostasis-and-regeneration-of-the-estrogen-receptor-positive-lineage
#19
Alexandra Van Keymeulen, Marco Fioramonti, Alessia Centonze, Gaëlle Bouvencourt, Younes Achouri, Cédric Blanpain
The mammary gland (MG) is composed of different cell lineages, including the basal and the luminal cells (LCs) that are maintained by distinct stem cell (SC) populations. LCs can be subdivided into estrogen receptor (ER)(+) and ER(-) cells. LCs act as the cancer cell of origin in different types of mammary tumors. It remains unclear whether the heterogeneity found in luminal-derived mammary tumors arises from a pre-existing heterogeneity within LCs. To investigate LC heterogeneity, we used lineage tracing to assess whether the ER(+) lineage is maintained by multipotent SCs or by lineage-restricted SCs...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813664/intestinal-dysbiosis-and-biotin-deprivation-induce-alopecia-through-overgrowth-of-lactobacillus-murinus-in-mice
#20
Atsushi Hayashi, Yohei Mikami, Kentaro Miyamoto, Nobuhiko Kamada, Toshiro Sato, Shinta Mizuno, Makoto Naganuma, Toshiaki Teratani, Ryo Aoki, Shinji Fukuda, Wataru Suda, Masahira Hattori, Masayuki Amagai, Manabu Ohyama, Takanori Kanai
Metabolism by the gut microbiota affects host physiology beyond the gastrointestinal tract. Here, we find that antibiotic-induced dysbiosis, in particular, overgrowth of Lactobacillus murinus (L. murinus), impaired gut metabolic function and led to the development of alopecia. While deprivation of dietary biotin per se did not affect skin physiology, its simultaneous treatment with vancomycin resulted in hair loss in specific pathogen-free (SPF) mice. Vancomycin treatment induced the accumulation of L. murinus in the gut, which consumes residual biotin and depletes available biotin in the gut...
August 15, 2017: Cell Reports
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