Cell: March 7, 2019 (Volume 176, Issue 6)

[Virtual Post Bioclues]

 

Mar 07, 2019 Vol. 176, Iss. 6 Website Table of Contents Online Now Archive

Highlights Announcements Free Webinar: The Immunotherapy Revolution: Towards Future Cancer Treatments Speakers: Elaine Mardis (The Ohio State University) and Jedd Wolchok (Memorial Sloan Kettering Cancer Center) March 19, 2019, 11:00 am ET Claim your free registration for live or on-demand access today! Click here to register. LabLinks: Single-Molecule Technologies for Proteins and Nucleic Acids Join us at this free LabLinks event on March 11, 2019, in New York. Register today! Free Webinar: High-Throughput Single-Molecule Technologies Speakers: Ilya Finkelstein (The University of Texas at Austin), Taekjip Ha (Johns Hopkins University) & Xiaowei Zhuang (Harvard University) March 27, 2019, 1:00 pm ET Register for live and on-demand access here. Click here to submit. Video Abstract Seq-ing Out AML States By combining transcriptomics with mutational profiles within the same cell an atlas of acute myeloid leukemia states is reported and reveals distinct functional subsets and their associated drivers. Cell Podcast Caught the flu? Eat fiber In this edition, we’ll hear about how heritability traits can be inferred from electronic medical records, with Nick Tatonetti and Fernanda Polubriaginof, Cell (00:00); why fiber does wonders for your immune system, with Benjamin Marsland, Immunity (9:56); and what’s behind the high- energy demands of mining Bitcoin, with Alex de Vries, Joule (18:56). Featured Article Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis Stratton and colleagues Featured Leading Edge Article VEGF in Signaling and Disease: Beyond Discovery and Development Ferrara and colleagues Focus Signaling and Disease This Cell Focus features The PI3K Pathway in Human Diseasefrom David Fruman, Lewis Cantley, Robert Abraham and colleagues. For more reviews on Signaling and Disease visit our Focus on the Cell website.

Table of Contents Leading Edge Previews An Error-Prone Polymerase in the Fight against Cancer Yathish Jagadheesh Achar, Marco Foiani Error-prone polymerases are alleged to induce mutations while replicating damaged DNA and to increase the risk of cancer. Using in vitro studies and mice models, Yoon et al. (2019) provide evidence that the error-prone Pol θ polymerase protects against ultraviolet light-induced skin cancer despite its mutagenic potential. Some Like it HOT: Horizontal Operon Transfer Amelia R.I. Lindsey, Irene L.G. Newton While horizontal gene transfer (HGT) is well documented in bacteria, the role and frequency of HGT across eukaryotes remains poorly understood. Kominek et al. identified a horizontal operon transfer (HOT) event, with clear evidence for selection to facilitate gene expression, that has allowed a group of yeasts to scavenge iron using bacterially derived genes. Self-Assembling Nanoparticles Usher in a New Era of Vaccine Design Rino Rappuoli, Davide Serruto In this issue, Marcandalli et al. (2019) report a self-assembling nanoparticle bearing an antigen from respiratory syncytial virus. This is the first time the structure, stability, and adjuvanticity of an antigen have been rationally designed at the atomic level and incorporated in one vaccine. Review VEGF in Signaling and Disease: Beyond Discovery and Development Rajendra S. Apte, Daniel S. Chen, Napoleone Ferrara Since it discovery two decades ago, VEGF has emerged as an important modulator of vascular biology, with therapeutics targeting VEGF signaling being central to the treatment of cancer and eye disease. Articles Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity Peter van Galen, Volker Hovestadt, Marc H. Wadsworth II, Travis K. Hughes, Gabriel K. Griffin, Sofia Battaglia, Julia A. Verga, Jason Stephansky, Timothy J. Pastika, Jennifer Lombardi Story, Geraldine S. Pinkus, Olga Pozdnyakova, Ilene Galinsky, Richard M. Stone, Timothy A. Graubert, Alex K. Shalek, Jon C. Aster, Andrew A. Lane, Bradley E. Bernstein A combination of transcriptomics and mutational analyses in single cells from acute myeloid leukemia patients reveals the existence of distinct functional subsets and their associated drivers. Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis Mia Petljak, Ludmil B. Alexandrov, Jonathan S. Brammeld, Stacey Price, David C. Wedge, Sebastian Grossmann, Kevin J. Dawson, Young Seok Ju, Francesco Iorio, Jose M.C. Tubio, Ching Chiek Koh, Ilias Georgakopoulos-Soares, Bernardo Rodríguez–Martín, Burçak Otlu, Sarah O’Meara, Adam P. Butler, Andrew Menzies, Shriram G. Bhosle, Keiran Raine, David R. Jones, Jon W. Teague, Kathryn Beal, Calli Latimer, Laura O’Neill, Jorge Zamora, Elizabeth Anderson, Nikita Patel, Mark Maddison, Bee Ling Ng, Jennifer Graham, Mathew J. Garnett, Ultan McDermott, Serena Nik-Zainal, Peter J. Campbell, Michael R. Stratton Open Access An analysis of 1,001 human cancer cell lines and 577 xenografts shows that mutagenesis associated with the cytodine deaminase APOBEC occurs in episodic bursts in contrast to mutation signatures associated with DNA replication and repair. Error-Prone Replication through UV Lesions by DNA Polymerase θ Protects against Skin Cancers Jung-Hoon Yoon, Mark J. McArthur, Jeseong Park, Debashree Basu, Maki Wakamiya, Louise Prakash, Satya Prakash Both error-free TLS by DNA polymerase η and error-prone TLS by DNA polymerase θ through UV lesions protect against replication stress-induced chromosomal instability and prevent skin cancer formation. Megabase Length Hypermutation Accompanies Human Structural Variation at 17p11.2 Christine R. Beck, Claudia M.B. Carvalho, Zeynep C. Akdemir, Fritz J. Sedlazeck, Xiaofei Song, Qingchang Meng, Jianhong Hu, Harsha Doddapaneni, Zechen Chong, Edward S. Chen, Philip C. Thornton, Pengfei Liu, Bo Yuan, Marjorie Withers, Shalini N. Jhangiani, Divya Kalra, Kimberly Walker, Adam C. English, Yi Han, Ken Chen, Donna M. Muzny, Grzegorz Ira, Chad A. Shaw, Richard A. Gibbs, P.J. Hastings, James R. Lupski Newly occurring structural variants within in human genomes spawn extensive, local single-nucleotide changes leading to an enhanced mutational burden within proximal genes. Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics Leif S. Ludwig, Caleb A. Lareau, Jacob C. Ulirsch, Elena Christian, Christoph Muus, Lauren H. Li, Karin Pelka, Will Ge, Yaara Oren, Alison Brack, Travis Law, Christopher Rodman, Jonathan H. Chen, Genevieve M. Boland, Nir Hacohen, Orit Rozenblatt-Rosen, Martin J. Aryee, Jason D. Buenrostro, Aviv Regev, Vijay G. Sankaran Using single-cell sequencing technologies, somatic mutations in mtDNA can be used as natural genetic barcodes to study cellular states and clonal dynamics. Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans Petra Bacher, Thordis Hohnstein, Eva Beerbaum, Marie Röcker, Matthew G. Blango, Svenja Kaufmann, Jobst Röhmel, Patience Eschenhagen, Claudia Grehn, Kathrin Seidel, Volker Rickerts, Laura Lozza, Ulrik Stervbo, Mikalai Nienen, Nina Babel, Julia Milleck, Mario Assenmacher, Oliver A. Cornely, Maren Ziegler, Hilmar Wisplinghoff, Guido Heine, Margitta Worm, Britta Siegmund, Jochen Maul, Petra Creutz, Christoph Tabeling, Christoph Ruwwe-Glösenkamp, Leif E. Sander, Christoph Knosalla, Sascha Brunke, Bernhard Hube, Olaf Kniemeyer, Axel A. Brakhage, Carsten Schwarz, Alexander Scheffold Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Eukaryotic Acquisition of a Bacterial Operon Jacek Kominek, Drew T. Doering, Dana A. Opulente, Xing-Xing Shen, Xiaofan Zhou, Jeremy DeVirgilio, Amanda B. Hulfachor, Marizeth Groenewald, Mcsean A. Mcgee, Steven D. Karlen, Cletus P. Kurtzman, Antonis Rokas, Chris Todd Hittinger Horizontal gene transfer of a full operon encoding siderophore biosynthesis genes from bacteria to a group of budding yeasts was followed by acquisition of eukaryotic genomic and transcriptional features. The Root Cap Cuticle: A Cell Wall Structure for Seedling Establishment and Lateral Root Formation Alice Berhin, Damien de Bellis, Rochus B. Franke, Rafael A. Buono, Moritz K. Nowack, Christiane Nawrath A cuticle-like cell wall structure on plant root caps protects seedlings from abiotic stress and contributes to proper lateral root outgrowth. Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity Peng Xia, Daniel Gütl, Vanessa Zheden, Carl-Philipp Heisenberg Specification of a single precursor cell fate in zebrafish oogenesis is mediated by lateral inhibition driven by mechanical forces that lead to nuclear exclusion of a developmental transcriptional activator in neighboring cells. A Hippocampus-Accumbens Tripartite Neuronal Motif Guides Appetitive Memory in Space Stéphanie Trouche, Vadim Koren, Natalie M. Doig, Tommas J. Ellender, Mohamady El-Gaby, Vítor Lopes-dos-Santos, Hayley M. Reeve, Pavel V. Perestenko, Farid N. Garas, Peter J. Magill, Andrew Sharott, David Dupret Open Access Retrieving and acting on memories of food-predicting environments are fundamental processes for animal survival. Trouche et al. show in mice that the behavioral manifestation of spatial appetitive memory requires a direct neural pathway from dorsal hippocampus to nucleus accumbens. This pathway engages dCA1 with a select population of accumbens parvalbumin-expressing fast-spiking interneurons, thereby sculpting the assembly activity of its postsynaptic medium-sized spiny neurons. An indirect pathway through dorsal subiculum is dispensable for appetitive memory but contributes to spatial novelty detection. Quiescence Modulates Stem Cell Maintenance and Regenerative Capacity in the Aging Brain Georgios Kalamakis, Daniel Brüne, Srikanth Ravichandran, Jan Bolz, Wenqiang Fan, Frederik Ziebell, Thomas Stiehl, Francisco Catalá-Martinez, Janina Kupke, Sheng Zhao, Enric Llorens-Bobadilla, Katharina Bauer, Stefanie Limpert, Birgit Berger, Urs Christen, Peter Schmezer, Jan Philipp Mallm, Benedikt Berninger, Simon Anders, Antonio del Sol, Anna Marciniak-Czochra, Ana Martin-Villalba Aged brains have a small number of highly quiescent neural stem cells that, upon activation, functionally resemble young stem cells; it is the niche itself that becomes more inflammatory and drives this quiescence. Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus Jessica Marcandalli, Brooke Fiala, Sebastian Ols, Michela Perotti, Willem de van der Schueren, Joost Snijder, Edgar Hodge, Mark Benhaim, Rashmi Ravichandran, Lauren Carter, Will Sheffler, Livia Brunner, Maria Lawrenz, Patrice Dubois, Antonio Lanzavecchia, Federica Sallusto, Kelly K. Lee, David Veesler, Colin E. Correnti, Lance J. Stewart, David Baker, Karin Loré, Laurent Perez, Neil P. King Open Access A computationally designed self-assembling nanoparticle that displays 20 copies of a trimeric viral protein induces potent neutralizing antibody responses. Phosphoinositide Interactions Position cGAS at the Plasma Membrane to Ensure Efficient Distinction between Self- and Viral DNA Katherine C. Barnett, Julia M. Coronas-Serna, Wen Zhou, Michael J. Ernandes, Anh Cao, Philip J. Kranzusch, Jonathan C. Kagan The innate immune receptor cGAS interacts with PI(4,5)P2 in order to localize to the plasma membrane, which is critical to prevent aberrant interferon responses to self-DNA under conditions of genotoxic stress, as well as to properly sense viral infections. Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity Jiang Dai, Yi-Jiao Huang, Xinhua He, Ming Zhao, Xinzheng Wang, Zhao-Shan Liu, Wen Xue, Hong Cai, Xiao-Yan Zhan, Shao-Yi Huang, Kun He, Hongxia Wang, Na Wang, Zhihong Sang, Tingting Li, Qiu-Ying Han, Jie Mao, Xinwei Diao, Nan Song, Yuan Chen, Wei-Hua Li, Jiang-Hong Man, Ai-Ling Li, Tao Zhou, Zheng-Gang Liu, Xue-Min Zhang, Tao Li Activation of the DNA sensor cGAS requires a deacetylation step, and its aspirin-induced acetylation can limit innate immune responses. Auto-regulation of Secretory Flux by Sensing and Responding to the Folded Cargo Protein Load in the Endoplasmic Reticulum Advait Subramanian, Anita Capalbo, Namrata Ravi Iyengar, Riccardo Rizzo, Antonella di Campli, Rosaria Di Martino, Matteo Lo Monte, Andrea R. Beccari, Amol Yerudkar, Carmen del Vecchio, Luigi Glielmo, Gabriele Turacchio, Marinella Pirozzi, Sang Geon Kim, Petra Henklein, Jorge Cancino, Seetharaman Parashuraman, Dario Diviani, Francesca Fanelli, Michele Sallese, Alberto Luini By sensing the load of folded ER lumenal proteins, the COPII subunit Sec24 directs a signaling cascade that allows secretory pathway flux to respond to the abundance of cargo. Higher-Order Clustering of the Transmembrane Anchor of DR5 Drives Signaling Liqiang Pan, Tian-Min Fu, Wenbin Zhao, Linlin Zhao, Wen Chen, Chixiao Qiu, Wenhui Liu, Zhijun Liu, Alessandro Piai, Qingshan Fu, Shuqing Chen, Hao Wu, James J. Chou Unlike traditional receptor clustering mediated by intracellular and extracellular domain oligomerization, the transmembrane domain alone of some TNF family receptors can form higher-order structures competent to drive signaling, basally inhibited by the unliganded ectodomain. Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L Evan J. Worden, Niklas A. Hoffmann, Chad W. Hicks, Cynthia Wolberger Unanticipated conformational plasticity in the globular core of histone H3 underlies cross-talk between histone modifications. Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization Elizabeth H. Finn, Gianluca Pegoraro, Hugo B. Brandão, Anne-Laure Valton, Marlies E. Oomen, Job Dekker, Leonid Mirny, Tom Misteli High-throughput imaging of several hundred chromatin interactions in individual cells reveals extensive heterogenity in spatial genome organization at the single-cell level. Corrections A Genome-wide Framework for Mapping Gene Regulation via Cellular Genetic Screens Molly Gasperini, Andrew J. Hill, José L. McFaline-Figueroa, Beth Martin, Seungsoo Kim, Melissa D. Zhang, Dana Jackson, Anh Leith, Jacob Schreiber, William S. Noble, Cole Trapnell, Nadav Ahituv, Jay Shendure Optimal-Transport Analysis of Single-Cell Gene Expression Identifies Developmental Trajectories in Reprogramming Geoffrey Schiebinger, Jian Shu, Marcin Tabaka, Brian Cleary, Vidya Subramanian, Aryeh Solomon, Joshua Gould, Siyan Liu, Stacie Lin, Peter Berube, Lia Lee, Jenny Chen, Justin Brumbaugh, Philippe Rigollet, Konrad Hochedlinger, Rudolf Jaenisch, Aviv Regev, Eric S. Lander Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome Yongdae Shin, Yi-Che Chang, Daniel S.W. Lee, Joel Berry, David W. Sanders, Pierre Ronceray, Ned S. Wingreen, Mikko Haataja, Clifford P. Brangwynne