Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis
Publication date: Available online 14 June 2018 Source:Cell Author(s): Paul K. Ziegler, Julia Bollrath, Charles K. Pallangyo, Takaji Matsutani, Özge Canli, Tiago De Oliveira, Michaela A. Diamanti, Nina Müller, Jaba Gamrekelashvili, Tracy Putoczki, David Horst, Arun K. Mankan, Meryem G. Öner, Susanna Müller, Josef Müller-Höcker, Thomas Kirchner, Julia Slotta-Huspenina, M. Mark Taketo, Thomas Reinheckel, Stefan Dröse, Andrew C. Larner, Winfried S. Wels, Matthias Ernst, Tim F. Greten, Melek C. Arkan, Thomas Korn, Dagmar Wirth, Florian R. Greten In colorectal cancer patients, a high density ...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

A Somatically Acquired Enhancer of the Androgen Receptor Is a Noncoding Driver in Advanced Prostate Cancer
Publication date: Available online 14 June 2018 Source:Cell Author(s): David Y. Takeda, Sándor Spisák, Ji-Heui Seo, Connor Bell, Edward O’Connor, Keegan Korthauer, Dezső Ribli, István Csabai, Norbert Solymosi, Zoltán Szállási, David R. Stillman, Paloma Cejas, Xintao Qiu, Henry W. Long, Viktória Tisza, Pier Vitale Nuzzo, Mersedeh Rohanizadegan, Mark M. Pomerantz, William C. Hahn, Matthew L. Freedman Increased androgen receptor (AR) activity drives therapeutic resistance in advanced prostate cancer. The most common resistance mechanism is amplification of this locus pr...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

A Milieu Molecule for TGF- β Required for Microglia Function in the Nervous System
Publication date: Available online 14 June 2018 Source:Cell Author(s): Yan Qin, Brian S. Garrison, Wenjiang Ma, Rui Wang, Aiping Jiang, Jing Li, Meeta Mistry, Roderick T. Bronson, Daria Santoro, Charlotte Franco, Daisy A. Robinton, Beth Stevens, Derrick J. Rossi, Chafen Lu, Timothy A. Springer Extracellular proTGF-β is covalently linked to “milieu” molecules in the matrix or on cell surfaces and is latent until TGF-β is released by integrins. Here, we show that LRRC33 on the surface of microglia functions as a milieu molecule and enables highly localized, integrin-αVβ8-dependent TGF-β...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Developmental Origin Governs CD8+ T Cell Fate Decisions during Infection
Publication date: Available online 14 June 2018 Source:Cell Author(s): Norah L. Smith, Ravi K. Patel, Arnold Reynaldi, Jennifer K. Grenier, Jocelyn Wang, Neva B. Watson, Kito Nzingha, Kristel J. Yee Mon, Seth A. Peng, Andrew Grimson, Miles P. Davenport, Brian D. Rudd Heterogeneity is a hallmark feature of the adaptive immune system in vertebrates. Following infection, naive T cells differentiate into various subsets of effector and memory T cells, which help to eliminate pathogens and maintain long-term immunity. The current model suggests there is a single lineage of naive T cells that give rise to differe...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Inactivation of CDK12 Delineates a Distinct Immunogenic Class of Advanced Prostate Cancer
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): Yi-Mi Wu, Marcin Cieślik, Robert J. Lonigro, Pankaj Vats, Melissa A. Reimers, Xuhong Cao, Yu Ning, Lisha Wang, Lakshmi P. Kunju, Navonil de Sarkar, Elisabeth I. Heath, Jonathan Chou, Felix Y. Feng, Peter S. Nelson, Johann S. de Bono, Weiping Zou, Bruce Montgomery, Ajjai Alva, Dan R. Robinson, Arul M. Chinnaiyan Using integrative genomic analysis of 360 metastatic castration-resistant prostate cancer (mCRPC) samples, we identified a novel subtype of prostate cancer typified by biallelic loss of CDK12 that is mutually exclusive with tumors driven by...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Transient Osmotic Perturbation Causes Long-Term Alteration to the Gut Microbiota
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): Carolina Tropini, Eli Lin Moss, Bryan Douglas Merrill, Katharine Michelle Ng, Steven Kyle Higginbottom, Ellen Pun Casavant, Carlos Gutierrez Gonzalez, Brayon Fremin, Donna Michelle Bouley, Joshua Eric Elias, Ami Siddharth Bhatt, Kerwyn Casey Huang, Justin Laine Sonnenburg Osmotic diarrhea is a prevalent condition in humans caused by food intolerance, malabsorption, and widespread laxative use. Here, we assess the resilience of the gut ecosystem to osmotic perturbation at multiple length and timescales using mice as model hosts. Osmotic stress cause...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics ConsortiumDouglas M.RuderferStephanRipkeAndrewMcQuillinJamesBoocockEli A.StahlJennifer M. WhiteheadPavlidesNiamhMullinsAlexander W.CharneyAnil P.S.OriLoes M. OldeLoohuisEnricoDomeniciAriannaDi FlorioSergiPapiolJanos L.KalmanVassilyTrubetskoyRolfAdolfssonIngridAgartzEsbenAgerboHudaAkilDiegoAlbaniMargotAlbusMartinAldaMadelineAlexanderNeyAlliey-RodriguezThomas D.AlsFarooqAminAdebayoAnjorinMaria J.ArranzSwapnilAwasthiSilviu A.BacanuJudith A.BadnerMarieBaekvad-HansenStevenBakke...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Helicase-Dependent RNA Decay Illuminated by a Cryo-EM Structure of a Human Nuclear RNA Exosome-MTR4 Complex
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): Eva-Maria Weick, M. Rhyan Puno, Kurt Januszyk, John C. Zinder, Michael A. DiMattia, Christopher D. Lima The ribonucleolytic RNA exosome interacts with RNA helicases to degrade RNA. To understand how the 3′ to 5′ Mtr4 helicase engages RNA and the nuclear exosome, we reconstituted 14-subunit Mtr4-containing RNA exosomes from Saccharomyces cerevisiae, Schizosaccharomyces pombe, and human and show that they unwind structured substrates to promote degradation. We loaded a human exosome with an optimized DNA-RNA chimera that stalls MTR4 ...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Prospectively Isolated Tetraspanin+ Neoblasts Are Adult Pluripotent Stem Cells Underlying Planaria Regeneration
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): An Zeng, Hua Li, Longhua Guo, Xin Gao, Sean McKinney, Yongfu Wang, Zulin Yu, Jungeun Park, Craig Semerad, Eric Ross, Li-Chun Cheng, Erin Davies, Kai Lei, Wei Wang, Anoja Perera, Kate Hall, Allison Peak, Andrew Box, Alejandro Sánchez Alvarado Proliferating cells known as neoblasts include pluripotent stem cells (PSCs) that sustain tissue homeostasis and regeneration of lost body parts in planarians. However, the lack of markers to prospectively identify and isolate these adult PSCs has significantly hampered their characterization. We used si...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Common Disease Is More Complex Than Implied by the Core Gene Omnigenic Model
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): Naomi R. Wray, Cisca Wijmenga, Patrick F. Sullivan, Jian Yang, Peter M. Visscher The evidence that most adult-onset common diseases have a polygenic genetic architecture fully consistent with robust biological systems supported by multiple back-up mechanisms is now overwhelming. In this context, we consider the recent “omnigenic” or “core genes” model. A key assumption of the model is that there is a relatively small number of core genes relevant to any disease. While intuitively appealing, this model may underestimate the b...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Sunlight Brightens Learning and Memory
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): Lynne Chantranupong, Bernardo L. Sabatini Sunlight can alter mood, behavior, and cognition, but the cellular basis of this phenomenon remains to be fully elucidated. In this issue of Cell, Zhu et al. shed light on a UV-dependent metabolic pathway that leads to increased synaptic release of glutamate and enhanced motor learning and memory in mice. Teaser Sunlight can alter mood, behavior, and cognition, but the cellular basis of this phenomenon remains to be fully elucidated. In this issue of Cell, Zhu et al. shed light on a UV-dependent m...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Disease Heritability Studies Harness the Healthcare System to Achieve Massive Scale
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): Joshua C. Denny, Jonathan D. Mosley Heritability studies are essential for defining genetic influences on disease risk and trait variability. Polubriaginof et al. show how massive amounts of data contained in electronic health records can be used for heritability studies on hundreds of phenotypes. Mining emergency contact information with comparison to existing gold standards showcases the broad utility of the approach. Teaser Heritability studies are essential for defining genetic influences on disease risk and trait variability. Polubriagino...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Prospecting for Planarian Pluripotency
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): Tania Rozario, Phillip A. Newmark Planarians are renowned for extraordinary regenerative abilities that are driven by stem cells maintained throughout their lives. In this issue of Cell, Zeng et al. report the prospective isolation of planarian pluripotent stem cells. Their work opens new directions for understanding how these remarkable cells are established, maintained, and activated. Teaser Planarians are renowned for extraordinary regenerative abilities that are driven by stem cells maintained throughout their lives. In this issue of Cell,...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Visible Machine Learning for Biomedicine
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): Michael K. Yu, Jianzhu Ma, Jasmin Fisher, Jason F. Kreisberg, Benjamin J. Raphael, Trey Ideker A major ambition of artificial intelligence lies in translating patient data to successful therapies. Machine learning models face particular challenges in biomedicine, however, including handling of extreme data heterogeneity and lack of mechanistic insight into predictions. Here, we argue for “visible” approaches that guide model structure with experimental biology. Teaser A major ambition of artificial intelligence lies in translating patie...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

CRISPR Inspirations
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 (Source: Cell)
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

The Ongoing Shakeup in Organelle Biology
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 With the complexities of organelle communication and their dynamics under intense investigation, what are the new principles that are emerging, and where is the field headed? Cell’s Robert Kruger recently discussed these questions with Erika Holzbaur, Jennifer Lippincott-Schwartz, and Ivan Dikic. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online. Teaser With the complexities of organelle communication and their dynamics under intense investigation, what are the new principles tha...
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

New Flavors in Immunomodulation
Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): Jacques Deguine (Source: Cell)
Source: Cell - June 15, 2018 Category: Cytology Source Type: research

Next-Generation Machine Learning for Biological Networks
Publication date: Available online 7 June 2018 Source:Cell Author(s): Diogo M. Camacho, Katherine M. Collins, Rani K. Powers, James C. Costello, James J. Collins Machine learning, a collection of data-analytical techniques aimed at building predictive models from multi-dimensional datasets, is becoming integral to modern biological research. By enabling one to generate models that learn from large datasets and make predictions on likely outcomes, machine learning can be used to study complex cellular systems such as biological networks. Here, we provide a primer on machine learning for life scientists, including an introd...
Source: Cell - June 7, 2018 Category: Cytology Source Type: research

TCR Transgenic Mice Reveal Stepwise, Multi-site Acquisition of the Distinctive Fat-Treg Phenotype
Publication date: Available online 7 June 2018 Source:Cell Author(s): Chaoran Li, Joanna R. DiSpirito, David Zemmour, Raul German Spallanzani, Wilson Kuswanto, Christophe Benoist, Diane Mathis Visceral adipose tissue (VAT) hosts a population of regulatory T (Treg) cells, with a unique phenotype, that controls local and systemic inflammation and metabolism. Generation of a T cell receptor transgenic mouse line, wherein VAT Tregs are highly enriched, facilitated study of their provenance, dependencies, and activities. We definitively established a role for T cell receptor specificity, uncovered an unexpected funct...
Source: Cell - June 7, 2018 Category: Cytology Source Type: research

Structural Basis for Transcript Elongation Control by NusG Family Universal Regulators
Publication date: Available online 7 June 2018 Source:Cell Author(s): Jin Young Kang, Rachel Anne Mooney, Yuri Nedialkov, Jason Saba, Tatiana V. Mishanina, Irina Artsimovitch, Robert Landick, Seth A. Darst NusG/RfaH/Spt5 transcription elongation factors are the only transcription regulators conserved across all life. Bacterial NusG regulates RNA polymerase (RNAP) elongation complexes (ECs) across most genes, enhancing elongation by suppressing RNAP backtracking and coordinating ρ-dependent termination and translation. The NusG paralog RfaH engages the EC only at operon polarity suppressor (ops) sites and suppress...
Source: Cell - June 7, 2018 Category: Cytology Source Type: research

Dynamics and Spatial Genomics of the Nascent Transcriptome by Intron seqFISH
Publication date: Available online 7 June 2018 Source:Cell Author(s): Sheel Shah, Yodai Takei, Wen Zhou, Eric Lubeck, Jina Yun, Chee-Huat Linus Eng, Noushin Koulena, Christopher Cronin, Christoph Karp, Eric J. Liaw, Mina Amin, Long Cai Visualization of the transcriptome and the nuclear organization in situ has been challenging for single-cell analysis. Here, we demonstrate a multiplexed single-molecule in situ method, intron seqFISH, that allows imaging of 10,421 genes at their nascent transcription active sites in single cells, followed by mRNA and lncRNA seqFISH and immunofluorescence. This nascent transcriptome-profili...
Source: Cell - June 7, 2018 Category: Cytology Source Type: research

Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus
Publication date: Available online 7 June 2018 Source:Cell Author(s): Sofia A. Quinodoz, Noah Ollikainen, Barbara Tabak, Ali Palla, Jan Marten Schmidt, Elizabeth Detmar, Mason M. Lai, Alexander A. Shishkin, Prashant Bhat, Yodai Takei, Vickie Trinh, Erik Aznauryan, Pamela Russell, Christine Cheng, Marko Jovanovic, Amy Chow, Long Cai, Patrick McDonel, Manuel Garber, Mitchell Guttman Eukaryotic genomes are packaged into a 3-dimensional structure in the nucleus. Current methods for studying genome-wide structure are based on proximity ligation. However, this approach can fail to detect known structures, such as interactions w...
Source: Cell - June 7, 2018 Category: Cytology Source Type: research

A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits
Publication date: Available online 7 June 2018 Source:Cell Author(s): Leonardo Almeida-Souza, Rene A.W. Frank, Javier García-Nafría, Adeline Colussi, Nushan Gunawardana, Christopher M. Johnson, Minmin Yu, Gillian Howard, Byron Andrews, Yvonne Vallis, Harvey T. McMahon Multiple proteins act co-operatively in mammalian clathrin-mediated endocytosis (CME) to generate endocytic vesicles from the plasma membrane. The principles controlling the activation and organization of the actin cytoskeleton during mammalian CME are, however, not fully understood. Here, we show that the protein FCHSD2 is a major activator of...
Source: Cell - June 7, 2018 Category: Cytology Source Type: research

A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling
We describe a metabolic sensing circuit that may have evolved to facilitate mutualistic responses to luminal pathosymbionts. Graphical abstract Teaser Succinate produced by mutualistic colonizing protozoa activates a small intestinal tuft cell-ILC2 circuit, leading to adaptive remodeling that facilitates energy homeostasis and infection resistance in the host and a reproductive niche for the pathosymbiont. (Source: Cell)
Source: Cell - June 7, 2018 Category: Cytology Source Type: research

A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain
Publication date: Available online 7 June 2018 Source:Cell Author(s): Benjamin Kleaveland, Charlie Y. Shi, Joanna Stefano, David P. Bartel Noncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more effective than previously desc...
Source: Cell - June 7, 2018 Category: Cytology Source Type: research

SMCHD1 Merges Chromosome Compartments and Assists Formation of Super-Structures on the Inactive X
We present a stepwise model for Xi folding, where SMCHD1 attenuates a hidden layer of Xi architecture to facilitate Xist spreading. Graphical abstract Teaser Mammalian X inactivation relies on stepwise folding of chromosome compartments. (Source: Cell)
Source: Cell - June 7, 2018 Category: Cytology Source Type: research

Acid Suspends the Circadian Clock in Hypoxia through Inhibition of mTOR
Publication date: Available online 31 May 2018 Source:Cell Author(s): Zandra E. Walton, Chirag H. Patel, Rebekah C. Brooks, Yongjun Yu, Arig Ibrahim-Hashim, Malini Riddle, Alessandra Porcu, Tianying Jiang, Brett L. Ecker, Feven Tameire, Constantinos Koumenis, Ashani T. Weeraratna, David K. Welsh, Robert Gillies, James C. Alwine, Lin Zhang, Jonathan D. Powell, Chi V. Dang Recent reports indicate that hypoxia influences the circadian clock through the transcriptional activities of hypoxia-inducible factors (HIFs) at clock genes. Unexpectedly, we uncover a profound disruption of the circadian clock and diurnal transcriptome ...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

SnapShot: Functions of Tubulin Posttranslational Modifications
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Maria M. Magiera, Puja Singh, Carsten Janke Post-translational modification of tubulin offers a mechanism for functional diversification of microtubules and regulation in a variety of physiological contexts. This SnapShot recaps the current state of understanding of tubulin posttranslational modifications and their functions in the regulation of biological processes. To view this SnapShot, open or download the PDF. Teaser Post-translational modification of tubulin offers a mechanism for functional diversification of microtubules and regulation in a ...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

Cnidarian Cell Type Diversity and Regulation Revealed by Whole-Organism Single-Cell RNA-Seq
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Arnau Sebé-Pedrós, Baptiste Saudemont, Elad Chomsky, Flora Plessier, Marie-Pierre Mailhé, Justine Renno, Yann Loe-Mie, Aviezer Lifshitz, Zohar Mukamel, Sandrine Schmutz, Sophie Novault, Patrick R.H. Steinmetz, François Spitz, Amos Tanay, Heather Marlow The emergence and diversification of cell types is a leading factor in animal evolution. So far, systematic characterization of the gene regulatory programs associated with cell type specificity was limited to few cell types and few species. Here, we perform whole-organism ...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

Genetic Inactivation of CD33 in Hematopoietic Stem Cells to Enable CAR T Cell Immunotherapy for Acute Myeloid Leukemia
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Miriam Y. Kim, Kyung-Rok Yu, Saad S. Kenderian, Marco Ruella, Shirley Chen, Tae-Hoon Shin, Aisha A. Aljanahi, Daniel Schreeder, Michael Klichinsky, Olga Shestova, Miroslaw S. Kozlowski, Katherine D. Cummins, Xinhe Shan, Maksim Shestov, Adam Bagg, Jennifer J.D. Morrissette, Palak Sekhri, Cicera R. Lazzarotto, Katherine R. Calvo, Douglas B. Kuhns, Robert E. Donahue, Gregory K. Behbehani, Shengdar Q. Tsai, Cynthia E. Dunbar, Saar Gill The absence of cancer-restricted surface markers is a major impediment to antigen-specific immunotherapy using chimeric...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

Human-Specific NOTCH2NL Genes Expand Cortical Neurogenesis through Delta/Notch Regulation
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Ikuo K. Suzuki, David Gacquer, Roxane Van Heurck, Devesh Kumar, Marta Wojno, Angéline Bilheu, Adèle Herpoel, Nelle Lambert, Julian Cheron, Franck Polleux, Vincent Detours, Pierre Vanderhaeghen The cerebral cortex underwent rapid expansion and increased complexity during recent hominid evolution. Gene duplications constitute a major evolutionary force, but their impact on human brain development remains unclear. Using tailored RNA sequencing (RNA-seq), we profiled the spatial and temporal expression of hominid-specific duplicated (...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Ian T. Fiddes, Gerrald A. Lodewijk, Meghan Mooring, Colleen M. Bosworth, Adam D. Ewing, Gary L. Mantalas, Adam M. Novak, Anouk van den Bout, Alex Bishara, Jimi L. Rosenkrantz, Ryan Lorig-Roach, Andrew R. Field, Maximilian Haeussler, Lotte Russo, Aparna Bhaduri, Tomasz J. Nowakowski, Alex A. Pollen, Max L. Dougherty, Xander Nuttle, Marie-Claude Addor, Simon Zwolinski, Sol Katzman, Arnold Kriegstein, Evan E. Eichler, Sofie R. Salama, Frank M.J. Jacobs, David Haussler Genetic changes causing brain size expansion in human evolution have remained elusive...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

A Fine-Scale Functional Logic to Convergence from Retina to Thalamus
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Liang Liang, Alex Fratzl, Glenn Goldey, Rohan N. Ramesh, Arthur U. Sugden, Josh L. Morgan, Chinfei Chen, Mark L. Andermann Numerous well-defined classes of retinal ganglion cells innervate the thalamus to guide image-forming vision, yet the rules governing their convergence and divergence remain unknown. Using two-photon calcium imaging in awake mouse thalamus, we observed a functional arrangement of retinal ganglion cell axonal boutons in which coarse-scale retinotopic ordering gives way to fine-scale organization based on shared preferences for ot...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

Tubulin Posttranslational Modifications and Emerging Links to Human Disease
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Maria M. Magiera, Puja Singh, Sudarshan Gadadhar, Carsten Janke Tubulin posttranslational modifications are currently emerging as important regulators of the microtubule cytoskeleton and thus have a strong potential to be implicated in a number of disorders. Here, we review the latest advances in understanding the physiological roles of tubulin modifications and their links to a variety of pathologies. Teaser Microtubules are decorated with posttranslational modifications that impact their cellular functions. This Review explores the emerging connec...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

Bracing for Abscission
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Anja Geitmann The detachment of plant organs is highly choreographed, requiring the enzymatic dissolution of the middle lamella between cell layers at the base of the detaching organ. Now, Lee et al. demonstrate that abscission efficiency and plant health rely on the spatial confinement of enzymatic activity and mechanical features that ensure a smooth separation. Teaser The detachment of plant organs is highly choreographed, requiring the enzymatic dissolution of the middle lamella between cell layers at the base of the detaching organ. Now, L...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

A “Counter-Enhancer” in Tumor Suppression
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Francesco P. Marchese, Maite Huarte The role of the noncoding genome in cancer biology is continually expanding. Cho et al. reveal a new and unexpected mechanism for the regulation of MYC expression mediated by the promoter sequence of its neighbor gene PVT1. This DNA element acts as a promoter-enhancer competitor and a candidate tumor suppressor. Teaser The role of the noncoding genome in cancer biology is continually expanding. Cho et al. reveal a new and unexpected mechanism for the regulation of MYC expression mediated by the promoter ...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

Increasing T Cell Versatility with SUPRA CARs
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Yvonne Y. Chen Chimeric antigen receptor (CAR) T cells offer a promising treatment option for advanced cancers resistant to standard therapy. Here, Cho et al. report a split-CAR design that enables the engineering of multi-feature CAR-T cells, aiming to address current challenges limiting the safety and efficacy of CAR-T cells for cancer treatment. Teaser Chimeric antigen receptor (CAR) T cells offer a promising treatment option for advanced cancers resistant to standard therapy. Here, Cho et al. report a split-CAR design that en...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

The Positives and Negatives of NPR: A Unifying Model for Salicylic Acid Signaling in Plants
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Roger Innes Salicylic acid (SA) is a potent inducer of defense gene expression in plants, but how SA activates transcription has been controversial. In this issue of Cell, Ding et al. show that the SA-binding proteins NPR3 and NPR4 function as transcriptional co-repressors, with this activity being blocked by SA. Teaser Salicylic acid (SA) is a potent inducer of defense gene expression in plants, but how SA activates transcription has been controversial. In this issue of Cell, Ding et al. show that the SA-binding proteins NPR3 and NPR4 fun...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

The Future of Genome Editing
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 The power of CRISPR is undeniable, but where is the field heading? Cell’s April Pawluk caught up with Jia Chen, Weizhi Ji, and Prashant Mali to discuss the successes and challenges we can expect in the coming years. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online. Teaser The power of CRISPR is undeniable, but where is the field heading? Cell’s April Pawluk caught up with Jia Chen, Weizhi Ji, and Prashant Mali to discuss the successes and challenges we can expect in the com...
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

Tracking Down and Interrogating Cancer ’s Holdouts
Publication date: 31 May 2018 Source:Cell, Volume 173, Issue 6 Author(s): Robert P. Kruger (Source: Cell)
Source: Cell - June 1, 2018 Category: Cytology Source Type: research

Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement
Publication date: Available online 24 May 2018 Source:Cell Author(s): Adar Adamsky, Adi Kol, Tirzah Kreisel, Adi Doron, Nofar Ozeri-Engelhard, Talia Melcer, Ron Refaeli, Henrike Horn, Limor Regev, Maya Groysman, Michael London, Inbal Goshen Astrocytes respond to neuronal activity and were shown to be necessary for plasticity and memory. To test whether astrocytic activity is also sufficient to generate synaptic potentiation and enhance memory, we expressed the Gq-coupled receptor hM3Dq in CA1 astrocytes, allowing their activation by a designer drug. We discovered that astrocytic activation is not only necessary for synapt...
Source: Cell - May 24, 2018 Category: Cytology Source Type: research

Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome
Publication date: Available online 24 May 2018 Source:Cell Author(s): Brian T. Weinert, Takeo Narita, Shankha Satpathy, Balaji Srinivasan, Bogi K. Hansen, Christian Schölz, William B. Hamilton, Beth E. Zucconi, Wesley W. Wang, Wenshe R. Liu, Joshua M. Brickman, Edward A. Kesicki, Albert Lai, Kenneth D. Bromberg, Philip A. Cole, Chunaram Choudhary The acetyltransferases CBP and p300 are multifunctional transcriptional co-activators. Here, we combined quantitative proteomics with CBP/p300-specific catalytic inhibitors, bromodomain inhibitor, and gene knockout to reveal a comprehensive map of regulated acetylation sites...
Source: Cell - May 24, 2018 Category: Cytology Source Type: research

The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet
Publication date: Available online 24 May 2018 Source:Cell Author(s): Christine A. Olson, Helen E. Vuong, Jessica M. Yano, Qingxing Y. Liang, David J. Nusbaum, Elaine Y. Hsiao The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here, we show that the gut microbiota is altered by the KD and required for protection against acute electrically induced seizures and spontaneous tonic-clonic seizures in two mouse models. Mice treated with antibiotics or reared germ free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiot...
Source: Cell - May 24, 2018 Category: Cytology Source Type: research

CTCF-Binding Elements Mediate Accessibility of RAG Substrates During Chromatin Scanning
We report that CBEs immediately downstream of frequently rearranged VH-RSSs increase recombination potential of their associated VH far beyond that provided by RSSs alone. This CBE activity becomes particularly striking upon IGCR1 inactivation, which allows RAG, likely via loop extrusion, to linearly scan chromatin far upstream. VH-associated CBEs stabilize interactions of D-proximal VHs first encountered by the DJHRC during linear RAG scanning and thereby promote dominant rearrangement of these VHs by an unanticipated chromatin accessibility-enhancing CBE function. Graphical abstract Teaser RAG endonuclease associated wit...
Source: Cell - May 24, 2018 Category: Cytology Source Type: research

Structural Basis of Smoothened Activation in Hedgehog Signaling
Publication date: Available online 24 May 2018 Source:Cell Author(s): Pengxiang Huang, Sanduo Zheng, Bradley M. Wierbowski, Youngchang Kim, Daniel Nedelcu, Laura Aravena, Jing Liu, Andrew C. Kruse, Adrian Salic The seven-transmembrane-spanning protein Smoothened is the central transducer in Hedgehog signaling, a pathway fundamental in development and in cancer. Smoothened is activated by cholesterol binding to its extracellular cysteine-rich domain (CRD). How this interaction leads to changes in the transmembrane domain and Smoothened activation is unknown. Here, we report crystal structures of sterol-activated Smoothened...
Source: Cell - May 24, 2018 Category: Cytology Source Type: research

An Activity Switch in Human Telomerase Based on RNA Conformation and Shaped by TCAB1
Publication date: Available online 24 May 2018 Source:Cell Author(s): Lu Chen, Caitlin M. Roake, Adam Freund, Pedro J. Batista, Siqi Tian, Yi A. Yin, Chandresh R. Gajera, Shengda Lin, Byron Lee, Matthew F. Pech, Andrew S. Venteicher, Rhiju Das, Howard Y. Chang, Steven E. Artandi Ribonucleoprotein enzymes require dynamic conformations of their RNA constituents for regulated catalysis. Human telomerase employs a non-coding RNA (hTR) with a bipartite arrangement of domains—a template-containing core and a distal three-way junction (CR4/5) that stimulates catalysis through unknown means. Here, we show that telomerase ac...
Source: Cell - May 24, 2018 Category: Cytology Source Type: research

Disease Heritability Inferred from Familial Relationships Reported in Medical Records
Publication date: Available online 17 May 2018 Source:Cell Author(s): Fernanda C.G. Polubriaginof, Rami Vanguri, Kayla Quinnies, Gillian M. Belbin, Alexandre Yahi, Hojjat Salmasian, Tal Lorberbaum, Victor Nw.wo, Li Li, Mark M. Shervey, Patricia Glowe, Iuliana Ionita-Laza, Mary Simmerling, George Hripcsak, Suzanne Bakken, David Goldstein, Krzysztof Kiryluk, Eimear E. Kenny, Joel Dudley, David K. Vawdrey, Nicholas P. Tatonetti Heritability is essential for understanding the biological causes of disease but requires laborious patient recruitment and phenotype ascertainment. Electronic health records (EHRs) passively capture ...
Source: Cell - May 18, 2018 Category: Cytology Source Type: research

The Eukaryotic Proteome Is Shaped by E3  Ubiquitin Ligases Targeting C-Terminal Degrons
Publication date: Available online 17 May 2018 Source:Cell Author(s): Itay Koren, Richard T. Timms, Tomasz Kula, Qikai Xu, Mamie Z. Li, Stephen J. Elledge Degrons are minimal elements that mediate the interaction of proteins with degradation machineries to promote proteolysis. Despite their central role in proteostasis, the number of known degrons remains small, and a facile technology to characterize them is lacking. Using a strategy combining global protein stability (GPS) profiling with a synthetic human peptidome, we identify thousands of peptides containing degron activity. Employing CRISPR screening, we establish th...
Source: Cell - May 18, 2018 Category: Cytology Source Type: research

Analysis of Genetically Diverse Macrophages Reveals Local and Domain-wide Mechanisms that Control Transcription Factor Binding and Function
Publication date: Available online 17 May 2018 Source:Cell Author(s): Verena M. Link, Sascha H. Duttke, Hyun B. Chun, Inge R. Holtman, Emma Westin, Marten A. Hoeksema, Yohei Abe, Dylan Skola, Casey E. Romanoski, Jenhan Tao, Gregory J. Fonseca, Ty D. Troutman, Nathanael J. Spann, Tobias Strid, Mashito Sakai, Miao Yu, Rong Hu, Rongxin Fang, Dirk Metzler, Bing Ren, Christopher K. Glass Non-coding genetic variation is a major driver of phenotypic diversity and allows the investigation of mechanisms that control gene expression. Here, we systematically investigated the effects of >50 million variations from five strains...
Source: Cell - May 18, 2018 Category: Cytology Source Type: research

Moderate UV Exposure Enhances Learning and Memory by Promoting a Novel Glutamate Biosynthetic Pathway in the Brain
Publication date: Available online 17 May 2018 Source:Cell Author(s): Hongying Zhu, Ning Wang, Lei Yao, Qi Chen, Ran Zhang, Junchao Qian, Yiwen Hou, Weiwei Guo, Sijia Fan, Siling Liu, Qiaoyun Zhao, Feng Du, Xin Zuo, Yujun Guo, Yan Xu, Jiali Li, Tian Xue, Kai Zhong, Xiaoyuan Song, Guangming Huang, Wei Xiong Sunlight exposure is known to affect mood, learning, and cognition. However, the molecular and cellular mechanisms remain elusive. Here, we show that moderate UV exposure elevated blood urocanic acid (UCA), which then crossed the blood-brain barrier. Single-cell mass spectrometry and isotopic labeling revealed a novel i...
Source: Cell - May 18, 2018 Category: Cytology Source Type: research