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Cell Reports

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https://www.readbyqxmd.com/read/27880917/phenotypic-and-interaction-profiling-of-the-human-phosphatases-identifies-diverse-mitotic-regulators
#1
Nicole St-Denis, Gagan D Gupta, Zhen Yuan Lin, Beatriz Gonzalez-Badillo, Amanda O Veri, James D R Knight, Dushyandi Rajendran, Amber L Couzens, Ko W Currie, Johnny M Tkach, Sally W T Cheung, Laurence Pelletier, Anne-Claude Gingras
Reversible phosphorylation is a fundamental regulatory mechanism, intricately coordinated by kinases and phosphatases, two classes of enzymes widely disrupted in human disease. To better understand the functions of the relatively understudied phosphatases, we have used complementary affinity purification and proximity-based interaction proteomics approaches to generate a physical interactome for 140 human proteins harboring phosphatase catalytic domains. We identified 1,335 high-confidence interactions (1,104 previously unreported), implicating these phosphatases in the regulation of a variety of cellular processes...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880916/nrl-regulated-transcriptome-dynamics-of-developing-rod-photoreceptors
#2
Jung-Woong Kim, Hyun-Jin Yang, Matthew John Brooks, Lina Zelinger, Gökhan Karakülah, Norimoto Gotoh, Alexis Boleda, Linn Gieser, Felipe Giuste, Dustin Thad Whitaker, Ashley Walton, Rafael Villasmil, Jennifer Joanna Barb, Peter Jonathan Munson, Koray Dogan Kaya, Vijender Chaitankar, Tiziana Cogliati, Anand Swaroop
Gene regulatory networks (GRNs) guiding differentiation of cell types and cell assemblies in the nervous system are poorly understood because of inherent complexities and interdependence of signaling pathways. Here, we report transcriptome dynamics of differentiating rod photoreceptors in the mammalian retina. Given that the transcription factor NRL determines rod cell fate, we performed expression profiling of developing NRL-positive (rods) and NRL-negative (S-cone-like) mouse photoreceptors. We identified a large-scale, sharp transition in the transcriptome landscape between postnatal days 6 and 10 concordant with rod morphogenesis...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880915/blunted-mglur-activation-disinhibits-striatopallidal-transmission-in-parkinsonian-mice
#3
Qiaoling Cui, Jason E Pitt, Arin Pamukcu, Jean-Francois Poulin, Omar S Mabrouk, Michael P Fiske, Isabel B Fan, Elizabeth C Augustine, Katherine A Young, Robert T Kennedy, Rajeshwar Awatramani, C Savio Chan
The prevailing circuit model predicts that hyperactivity of the striatopallidal pathway and subsequently increased inhibition of external globus pallidus (GPe) neurons lead to the hypokinetic symptoms of Parkinson's disease (PD). It is believed that hyperactivity of the striatopallidal pathway is due to inactivity of dopamine receptors on the somatodendritic membrane of striatopallidal neurons, but the exact cellular underpinnings remain unclear. In this study, we show that mouse GPe astrocytes critically control ambient glutamate level, which in turn gates striatopallidal transmission via the activation of presynaptic metabotropic glutamate receptors...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880914/neuronal-ctcf-is-necessary-for-basal-and-experience-dependent-gene-regulation-memory-formation-and-genomic-structure-of-bdnf-and-arc
#4
Dev Sharan Sams, Stefano Nardone, Dmitriy Getselter, Dana Raz, Moran Tal, Prudhvi Raj Rayi, Hanoch Kaphzan, Ofir Hakim, Evan Elliott
CCCTC-binding factor (CTCF) is an organizer of higher-order chromatin structure and regulates gene expression. Genetic studies have implicated mutations in CTCF in intellectual disabilities. However, the role of CTCF-mediated chromatin structure in learning and memory is unclear. We show that depletion of CTCF in postmitotic neurons, or depletion in the hippocampus of adult mice through viral-mediated knockout, induces deficits in learning and memory. These deficits in learning and memory at the beginning of adulthood are correlated with impaired long-term potentiation and reduced spine density, with no changes in basal synaptic transmission and dendritic morphogenesis and arborization...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880913/mdia-and-rock-mediate-actin-dependent-presynaptic-remodeling-regulating-synaptic-efficacy-and-anxiety
#5
Yuichi Deguchi, Masaya Harada, Ryota Shinohara, Michael Lazarus, Yoan Cherasse, Yoshihiro Urade, Daisuke Yamada, Masayuki Sekiguchi, Dai Watanabe, Tomoyuki Furuyashiki, Shuh Narumiya
Here, we show neuronal inactivation-induced presynaptic remodeling and involvement of the mammalian homolog of Diaphanous (mDia) and Rho-associated coiled-coil-containing kinase (ROCK), Rho-regulated modulators of actin and myosin, in this process. We find that social isolation induces inactivation of nucleus accumbens (NAc) neurons associated with elevated anxiety-like behavior, and that mDia in NAc neurons is essential in this process. Upon inactivation of cultured neurons, mDia induces circumferential actin filaments around the edge of the synaptic cleft, which contract the presynaptic terminals in a ROCK-dependent manner...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880912/cenp-a-is-dispensable-for-mitotic-centromere-function-after-initial-centromere-kinetochore-assembly
#6
Sebastian Hoffmann, Marie Dumont, Viviana Barra, Peter Ly, Yael Nechemia-Arbely, Moira A McMahon, Solène Hervé, Don W Cleveland, Daniele Fachinetti
Human centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete degradation of endogenous CENP-A, we now demonstrate that once the first steps of centromere assembly have been completed in G1/S, continued CENP-A binding is not required for maintaining kinetochore attachment to centromeres or for centromere function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby producing defective kinetochores and failure of chromosome segregation...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880911/usp44-is-an-integral-component-of-n-cor-that-contributes-to-gene-repression-by-deubiquitinating-histone-h2b
#7
Xianjiang Lan, Boyko S Atanassov, Wenqian Li, Ying Zhang, Laurence Florens, Ryan D Mohan, Paul J Galardy, Michael P Washburn, Jerry L Workman, Sharon Y R Dent
Decreased expression of the USP44 deubiquitinase has been associated with global increases in H2Bub1 levels during mouse embryonic stem cell (mESC) differentiation. However, whether USP44 directly deubiquitinates histone H2B or how its activity is targeted to chromatin is not known. We identified USP44 as an integral subunit of the nuclear receptor co-repressor (N-CoR) complex. USP44 within N-CoR deubiquitinates H2B in vitro and in vivo, and ablation of USP44 impairs the repressive activity of the N-CoR complex...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880910/cdk12-inhibition-reverses-de-novo-and-acquired-parp-inhibitor-resistance-in-brca-wild-type-and-mutated-models-of-triple-negative-breast-cancer
#8
Shawn F Johnson, Cristina Cruz, Ann Katrin Greifenberg, Sofia Dust, Daniel G Stover, David Chi, Benjamin Primack, Shiliang Cao, Andrea J Bernhardy, Rhiannon Coulson, Jean-Bernard Lazaro, Bose Kochupurakkal, Heather Sun, Christine Unitt, Lisa A Moreau, Kristopher A Sarosiek, Maurizio Scaltriti, Dejan Juric, José Baselga, Andrea L Richardson, Scott J Rodig, Alan D D'Andrea, Judith Balmaña, Neil Johnson, Matthias Geyer, Violeta Serra, Elgene Lim, Geoffrey I Shapiro
Although poly(ADP-ribose) polymerase (PARP) inhibitors are active in homologous recombination (HR)-deficient cancers, their utility is limited by acquired resistance after restoration of HR. Here, we report that dinaciclib, an inhibitor of cyclin-dependent kinases (CDKs) 1, 2, 5, and 9, additionally has potent activity against CDK12, a transcriptional regulator of HR. In BRCA-mutated triple-negative breast cancer (TNBC) cells and patient-derived xenografts (PDXs), dinaciclib ablates restored HR and reverses PARP inhibitor resistance...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880909/nfix-induces-a-switch-in-sox6-transcriptional-activity-to-regulate-myhc-i-expression-in-fetal-muscle
#9
Valentina Taglietti, Giovanni Maroli, Solei Cermenati, Stefania Monteverde, Andrea Ferrante, Giuliana Rossi, Giulio Cossu, Monica Beltrame, Graziella Messina
Sox6 belongs to the Sox gene family and plays a pivotal role in fiber type differentiation, suppressing transcription of slow-fiber-specific genes during fetal development. Here, we show that Sox6 plays opposite roles in MyHC-I regulation, acting as a positive and negative regulator of MyHC-I expression during embryonic and fetal myogenesis, respectively. During embryonic myogenesis, Sox6 positively regulates MyHC-I via transcriptional activation of Mef2C, whereas during fetal myogenesis, Sox6 requires and cooperates with the transcription factor Nfix in repressing MyHC-I expression...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880908/conditional-loss-of-pten-in-myogenic-progenitors-leads-to-postnatal-skeletal-muscle-hypertrophy-but-age-dependent-exhaustion-of-satellite-cells
#10
Feng Yue, Pengpeng Bi, Chao Wang, Jie Li, Xiaoqi Liu, Shihuan Kuang
Skeletal muscle stem cells (satellite cells [SCs]) are normally maintained in a quiescent (G0) state. Muscle injury not only activates SCs locally, but also alerts SCs in distant uninjured muscles via circulating factors. The resulting GAlert SCs are adapted to regenerative cues and regenerate injured muscles more efficiently, but whether they provide any long-term benefits to SCs is unknown. Here, we report that embryonic myogenic progenitors lacking the phosphatase and tensin homolog (Pten) exhibit enhanced proliferation and differentiation, resulting in muscle hypertrophy but fewer SCs in adult muscles...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880907/tet3-mediated-dna-demethylation-contributes-to-the-direct-conversion-of-fibroblast-to-functional-neuron
#11
Juan Zhang, Shuangquan Chen, Dongming Zhang, Zixiao Shi, Hong Li, Tongbiao Zhao, Baoyang Hu, Qi Zhou, Jianwei Jiao
The direct conversion of somatic cells to neurons by bypassing the multipotent cell state may be a powerful approach for personalized medicine. In addition to neuronal transcription factors and multiple small molecules, we find that epigenetic modification also contributes to the direct conversion of fibroblasts to neurons. Here, we show that Tet3, a DNA dioxygenase, can rapidly and efficiently convert fibroblasts directly into functional neurons. The induced neurons (iNs) express pan and mature neuronal markers such as Tuj1, Synapsin, and neuronal nuclei (NeuN)...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880906/emergence-of-a-wave-of-wnt-signaling-that-regulates-lung-alveologenesis-by-controlling-epithelial-self-renewal-and-differentiation
#12
David B Frank, Tien Peng, Jarod A Zepp, Melinda Snitow, Tiffaney L Vincent, Ian J Penkala, Zheng Cui, Michael J Herriges, Michael P Morley, Su Zhou, Min Min Lu, Edward E Morrisey
Alveologenesis is the culmination of lung development and involves the correct temporal and spatial signals to generate the delicate gas exchange interface required for respiration. Using a Wnt-signaling reporter system, we demonstrate the emergence of a Wnt-responsive alveolar epithelial cell sublineage, which arises during alveologenesis, called the axin2+ alveolar type 2 cell, or AT2(Axin2). The number of AT2(Axin2) cells increases substantially during late lung development, correlating with a wave of Wnt signaling during alveologenesis...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880905/semaphorin-3g-provides-a-repulsive-guidance-cue-to-lymphatic-endothelial-cells-via-neuropilin-2-plexind1
#13
Xinyi Liu, Akiyoshi Uemura, Yoko Fukushima, Yutaka Yoshida, Masanori Hirashima
The vertebrate circulatory system is composed of closely related blood and lymphatic vessels. It has been shown that lymphatic vascular patterning is regulated by blood vessels during development, but its molecular mechanisms have not been fully elucidated. Here, we show that the artery-derived ligand semaphorin 3G (Sema3G) and the endothelial cell receptor PlexinD1 play a role in lymphatic vascular patterning. In mouse embryonic back skin, genetic inactivation of Sema3G or PlexinD1 results in abnormal artery-lymph alignment and reduced lymphatic vascular branching...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880904/lyve1-marks-the-divergence-of-yolk-sac-definitive-hemogenic-endothelium-from-the-primitive-erythroid-lineage
#14
Lydia K Lee, Yasamine Ghorbanian, Wenyuan Wang, Yanling Wang, Yeon Joo Kim, Irving L Weissman, Matthew A Inlay, Hanna K A Mikkola
The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YS HSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880903/mirnas-are-essential-for-the-regulation-of-the-pi3k-akt-foxo-pathway-and-receptor-editing-during-b%C3%A2-cell-maturation
#15
Maryaline Coffre, David Benhamou, David Rieß, Lili Blumenberg, Valentina Snetkova, Marcus J Hines, Tirtha Chakraborty, Sofia Bajwa, Kari Jensen, Mark M W Chong, Lelise Getu, Gregg J Silverman, Robert Blelloch, Dan R Littman, Dinis Calado, Doron Melamed, Jane A Skok, Klaus Rajewsky, Sergei B Koralov
B cell development is a tightly regulated process dependent on sequential rearrangements of immunoglobulin loci that encode the antigen receptor. To elucidate the role of microRNAs (miRNAs) in the orchestration of B cell development, we ablated all miRNAs at the earliest stage of B cell development by conditionally targeting the enzymes critical for RNAi in early B cell precursors. Absence of any one of these enzymes led to a block at the pro- to pre-B cell transition due to increased apoptosis and a failure of pre-B cells to proliferate...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880902/forward-genetic-screens-in-zebrafish-identify-pre-mrna-processing-pathways-regulating-early-t-cell-development
#16
Norimasa Iwanami, Katarzyna Sikora, Andreas S Richter, Maren Mönnich, Lucia Guerri, Cristian Soza-Ried, Divine-Fondzenyuy Lawir, Fernando Mateos, Isabell Hess, Connor P O'Meara, Michael Schorpp, Thomas Boehm
Lymphocytes represent basic components of vertebrate adaptive immune systems, suggesting the utility of non-mammalian models to define the molecular basis of their development and differentiation. Our forward genetic screens in zebrafish for recessive mutations affecting early T cell development revealed several major genetic pathways. The identification of lineage-specific transcription factors and specific components of cytokine signaling and DNA replication and/or repair pathways known from studies of immunocompromised mammals provided an evolutionary cross-validation of the screen design...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880901/stress-kinase-gcn2-controls-the-proliferative-fitness-and-trafficking-of-cytotoxic-t-cells-independent-of-environmental-amino-acid-sensing
#17
Lee-Ann Van de Velde, Xi-Zhi J Guo, Lidija Barbaric, Amber M Smith, Thomas H Oguin, Paul G Thomas, Peter J Murray
GCN2 is one of four "stress kinases" that block translation by phosphorylating eIF2α. GCN2 is thought to bind uncharged tRNAs to "sense" amino acid availability. In mammals, myeloid cells expressing indoleamine dioxygenases locally deplete tryptophan, which is detected by GCN2 in T cells to cause proliferative arrest. GCN2-deficient T cells were reported to ectopically enter the cell cycle when tryptophan was limiting. Using GCN2-deficient strains crossed to T cell receptor (TCR) transgenic backgrounds, we found GCN2 is essential for induction of stress target genes such as CHOP...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880900/tailored-tumor-immunogenicity-reveals-regulation-of-cd4-and-cd8%C3%A2-t-cell-responses-against-cancer
#18
Sarah Knocke, Bettina Fleischmann-Mundt, Michael Saborowski, Michael P Manns, Florian Kühnel, Thomas C Wirth, Norman Woller
CD4 and CD8 T cells play a pivotal role in controlling tumor growth. However, the interplay of both cell types and their role in tumor suppression still remain elusive. In this study, we investigated the regulation of CD4 and CD8 T cell responses to different classes of tumor-specific antigens in liver cancer mouse models. Tumors were induced in p19Arf-deficient mice by hydrodynamic injection of transposon plasmids encoding NrasG12V and pre-defined tumor antigens. This allowed for assessing the regulation of tumor-specific CD4 and CD8 T cell responses...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880899/lc3c-contributes-to-vpu-mediated-antagonism-of-bst2-tetherin-restriction-on-hiv-1-release-through-a-non-canonical-autophagy-pathway
#19
Ursula Madjo, Olivier Leymarie, Stéphane Frémont, Aurelia Kuster, Mélanie Nehlich, Sarah Gallois-Montbrun, Katy Janvier, Clarisse Berlioz-Torrent
BST2 (bone marrow stromal antigen 2)/tetherin is a restriction factor of enveloped viruses, which blocks the release of viral particles. HIV-1 encodes proteins that antagonize this innate barrier, including the accessory protein Vpu. Here, we investigate whether the autophagy pathway and/or ATG proteins are hijacked by HIV-1 Vpu to circumvent BST2 restriction of viral release. We report that BST2 and Vpu are present in LC3-positive compartments. We found that Vpu selectively interacts with the ATG8 ortholog LC3C through the Vpu L63VEM66 sequence...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880898/hiv-1-control-by-nk-cells-via-reduced-interaction-between-kir2dl2-and-hla-c-%C3%A2-12-02-c-%C3%A2-14-03
#20
Zhansong Lin, Kimiko Kuroki, Nozomi Kuse, Xiaoming Sun, Tomohiro Akahoshi, Ying Qi, Takayuki Chikata, Takuya Naruto, Madoka Koyanagi, Hayato Murakoshi, Hiroyuki Gatanaga, Shinichi Oka, Mary Carrington, Katsumi Maenaka, Masafumi Takiguchi
Natural killer (NK) cells control viral infection in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands. We investigated 504 anti-retroviral (ART)-free Japanese patients chronically infected with HIV-1 and identified two KIR/HLA combinations, KIR2DL2/HLA-C(∗)12:02 and KIR2DL2/HLA-C(∗)14:03, that impact suppression of HIV-1 replication. KIR2DL2(+) NK cells suppressed viral replication in HLA-C(∗)14:03(+) or HLA-C(∗)12:02(+) cells to a significantly greater extent than did KIR2DL2(-) NK cells in vitro...
November 22, 2016: Cell Reports
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