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Cell
This journal offers authors two options (open access or subscription) to publish research

Aug 20, 2020

Volume 182Issue 4p787-1066
Open Archive
On the cover: Amyloid plaques associated with Alzheimer's disease (AD) are sites of complex cellular interactions. In this issue, Chen et al. (976–991) investigate the transcriptional changes occurring in tissue domains in a 100-µm diameter around amyloid plaques in an AD mouse model using spatial transcriptomics. The cover image shows an artistic interpretation of the in situ sequencing data in areas around the plaque, much like a topographical map, in which the amyloid plaques are at the top of the hill. Artist: Duygu Koldere Vilain....
On the cover: Amyloid plaques associated with Alzheimer's disease (AD) are sites of complex cellular interactions. In this issue, Chen et al. (976–991) investigate the transcriptional changes occurring in tissue domains in a 100-µm diameter around amyloid plaques in an AD mouse model using spatial transcriptomics. The cover image shows an artistic interpretation of the in situ sequencing data in areas around the plaque, much like a topographical map, in which the amyloid plaques are at the top of the hill. Artist: Duygu Koldere Vilain.

Leading Edge

Benchmarks

  • Rosalind Franklin and the Advent of Molecular Biology

    • Patrick Cramer
    Rosalind Franklin provided the key data for deriving the double helix structure of DNA. The English chemist also pioneered structural studies of colloids, viruses, and RNA. To celebrate the 100th anniversary of Franklin’s birth, I summarize her work, which shaped the emerging discipline of molecular biology.

Commentary

  • Travel Less. Make It Worthwhile.

    • Anja Geitmann
    Academic travel has a substantial carbon footprint. The ongoing pandemic has propelled the development and adoption of technologies for online delivery of seminars and remote attendance at scientific conferences. This should not lead to the complete elimination of in-person events, but the scientific community must seize the opportunity to permanently change its modus operandi and reduce the impact of its activities on the environment.

Previews

  • Making Sense of Mutation: What D614G Means for the COVID-19 Pandemic Remains Unclear

    • Nathan D. Grubaugh,
    • William P. Hanage,
    • Angela L. Rasmussen
    In this issue of Cell, Korber et al. found that a SARS-CoV-2 variant in the spike protein D614G rapidly became dominant around the world. Although clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.
  • Myeloid Cells TREM Down Anti-tumor Responses

    • Aimée Bugler-Lamb,
    • Martin Guilliams
    In this issue of Cell, Molgora et al. and Katzenelenbogen, Sheban, Yalin, et al. highlight the novel role of TREM2 in shaping the immunosuppressive profile of tumor-associated myeloid cells and report that complementing immune-checkpoint therapy with TREM2 blockade induces stronger anti-tumor immune responses and reduces tumor growth.

Perspective

Articles

  • Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus

    • Bette Korber,
    • Will M. Fischer,
    • Sandrasegaram Gnanakaran,
    • Hyejin Yoon,
    • James Theiler,
    • Werner Abfalterer,
    • Nick Hengartner,
    • Elena E. Giorgi,
    • Tanmoy Bhattacharya,
    • Brian Foley,
    • Kathryn M. Hastie,
    • Matthew D. Parker,
    • David G. Partridge,
    • Cariad M. Evans,
    • Timothy M. Freeman,
    • Thushan I. de Silva,
    • on behalf of the Sheffield COVID-19 Genomics Group,
    • Charlene McDanal,
    • Lautaro G. Perez,
    • Haili Tang,
    • Alex Moon-Walker,
    • Sean P. Whelan,
    • Celia C. LaBranche,
    • Erica O. Saphire,
    • David C. Montefiori
    Korber et al. present evidence that there are now more SARS-CoV-2 viruses circulating in the human population globally that have the G614 form of the Spike protein versus the D614 form that was originally identified from the first human cases in Wuhan, China. Follow-up studies show that patients infected with G614 shed more viral nucleic acid compared with those with D614, and G614-bearing viruses show significantly higher infectious titers in vitro than their D614 counterparts.
  • Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

    • Christopher O. Barnes,
    • Anthony P. West Jr.,
    • Kathryn E. Huey-Tubman,
    • Magnus A.G. Hoffmann,
    • Naima G. Sharaf,
    • Pauline R. Hoffman,
    • Nicholas Koranda,
    • Harry B. Gristick,
    • Christian Gaebler,
    • Frauke Muecksch,
    • Julio C. Cetrulo Lorenzi,
    • Shlomo Finkin,
    • Thomas Hägglöf,
    • Arlene Hurley,
    • Katrina G. Millard,
    • Yiska Weisblum,
    • Fabian Schmidt,
    • Theodora Hatziioannou,
    • Paul D. Bieniasz,
    • Marina Caskey,
    • Davide F. Robbiani,
    • Michel C. Nussenzweig,
    • Pamela J. Bjorkman
    Analysis of plasma from recovering COVID-19 patients identifies common features of antibodies that determine protection.
  • Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients

    • Christoph Kreer,
    • Matthias Zehner,
    • Timm Weber,
    • Meryem S. Ercanoglu,
    • Lutz Gieselmann,
    • Cornelius Rohde,
    • Sandro Halwe,
    • Michael Korenkov,
    • Philipp Schommers,
    • Kanika Vanshylla,
    • Veronica Di Cristanziano,
    • Hanna Janicki,
    • Reinhild Brinker,
    • Artem Ashurov,
    • Verena Krähling,
    • Alexandra Kupke,
    • Hadas Cohen-Dvashi,
    • Manuel Koch,
    • Jan Mathis Eckert,
    • Simone Lederer,
    • Nico Pfeifer,
    • Timo Wolf,
    • Maria J.G.T. Vehreschild,
    • Clemens Wendtner,
    • Ron Diskin,
    • Henning Gruell,
    • Stephan Becker,
    • Florian Klein
    In a longitudinal analysis of SARS-CoV-2-infected people, Kreer et al. find highly potent neutralizing antibodies that use a broad spectrum of variable (V) genes and show low levels of somatic mutations. They also identify potential precursor sequences of these SARS-CoV-2-neutralizing antibodies from virus-naive individuals, sampled before the COVID-19 pandemic. This could indicate that neutralizing antibodies can be readily generated from existing germline antibody sequences found in the general population.
  • Multiple Signaling Roles of CD3ε and Its Application in CAR-T Cell Therapy

    • Wei Wu,
    • Qiuping Zhou,
    • Takeya Masubuchi,
    • Xiaoshan Shi,
    • Hua Li,
    • Xinyi Xu,
    • Min Huang,
    • Li Meng,
    • Xing He,
    • Hengyu Zhu,
    • Shuaixin Gao,
    • Nan Zhang,
    • Ruirui Jing,
    • Jie Sun,
    • Haopeng Wang,
    • Enfu Hui,
    • Catherine Chiulan Wong,
    • Chenqi Xu
    CD3ε contains multiple motifs that regulate TCR signaling. A CAR-T design incorporating the CD3ε cytoplasmic domain shows reduced cytokine production and enhanced persistence, suggesting the potential of increasing CD3 diversity as a design strategy for improving CAR-T therapy.
  • Coupled scRNA-Seq and Intracellular Protein Activity Reveal an Immunosuppressive Role of TREM2 in Cancer

    • Yonatan Katzenelenbogen,
    • Fadi Sheban,
    • Adam Yalin,
    • Ido Yofe,
    • Dmitry Svetlichnyy,
    • Diego Adhemar Jaitin,
    • Chamutal Bornstein,
    • Adi Moshe,
    • Hadas Keren-Shaul,
    • Merav Cohen,
    • Shuang-Yin Wang,
    • Baoguo Li,
    • Eyal David,
    • Tomer-Meir Salame,
    • Assaf Weiner,
    • Ido Amit
    INs-seq, an integrated technology for scRNA-seq and intracellular protein activity uncovers a novel Arg1+ Trem2+ regulatory myeloid cells (Mreg), genetic ablation of Trem2 inhibits the accumulation of intra-tumoral Mreg, leading to immune reactivation and reduced tumor growth.
  • TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy

    • Martina Molgora,
    • Ekaterina Esaulova,
    • William Vermi,
    • Jinchao Hou,
    • Yun Chen,
    • Jingqin Luo,
    • Simone Brioschi,
    • Mattia Bugatti,
    • Andrea Salvatore Omodei,
    • Biancamaria Ricci,
    • Catrina Fronick,
    • Santosh K. Panda,
    • Yoshiko Takeuchi,
    • Matthew M. Gubin,
    • Roberta Faccio,
    • Marina Cella,
    • Susan Gilfillan,
    • Emil R. Unanue,
    • Maxim N. Artyomov,
    • Robert D. Schreiber,
    • Marco Colonna
    TREM2 is a pro-tumorigenic marker of tumor-infiltrating macrophages in mouse models and human tumors that can be targeted to curb tumor growth and improve the efficacy of checkpoint blockade therapy while remodeling the landscape of tumor-infiltrating macrophages.
  • The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Axis

    • Emma S. Winkler,
    • Swathi Shrihari,
    • Barry L. Hykes Jr.,
    • Scott A. Handley,
    • Prabhakar S. Andhey,
    • Yan-Jang S. Huang,
    • Amanda Swain,
    • Lindsay Droit,
    • Kranthi K. Chebrolu,
    • Matthias Mack,
    • Dana L. Vanlandingham,
    • Larissa B. Thackray,
    • Marina Cella,
    • Marco Colonna,
    • Maxim N. Artyomov,
    • Thaddeus S. Stappenbeck,
    • Michael S. Diamond
    Winkler et al. demonstrate that the intestinal microbiome modulates innate immunity to control alphavirus infection of circulating monocytes. Microbiome perturbation dampens TLR7-MyD88 responses in pDCs, blunting type I IFN production and monocyte ISG expression. A single Clostridium species or its associated secondary bile acid restores antiviral responses to inhibit CHIKV infection.
  • Extracellular DNA Promotes Efficient Extracellular Electron Transfer by Pyocyanin in Pseudomonas aeruginosa Biofilms

    • Scott H. Saunders,
    • Edmund C.M. Tse,
    • Matthew D. Yates,
    • Fernanda Jiménez Otero,
    • Scott A. Trammell,
    • Eric D.A. Stemp,
    • Jacqueline K. Barton,
    • Leonard M. Tender,
    • Dianne K. Newman
    Phenazines are retained in biofilms through binding to extracellular DNA, and together these biofilm components mediate efficient extracellular electron transfer to support bacterial metabolism
  • Converting Escherichia coli to a Synthetic Methylotroph Growing Solely on Methanol

    • Frederic Y.-H. Chen,
    • Hsin-Wei Jung,
    • Chao-Yin Tsuei,
    • James C. Liao
    Chen et al. demonstrate genetic reprogramming of E. coli to efficiently grow with methanol as the sole carbon source.
  • Memory Sequencing Reveals Heritable Single-Cell Gene Expression Programs Associated with Distinct Cellular Behaviors

    • Sydney M. Shaffer,
    • Benjamin L. Emert,
    • Raúl A. Reyes Hueros,
    • Christopher Cote,
    • Guillaume Harmange,
    • Dylan L. Schaff,
    • Ann E. Sizemore,
    • Rohit Gupte,
    • Eduardo Torre,
    • Abhyudai Singh,
    • Danielle S. Bassett,
    • Arjun Raj
    MemorySeq shows that in single cells, the expression pattern of some genes co-fluctuates slowly and is heritable, leading to subpopulations of cells with distinct behaviors, such as resistance to cancer drugs.
  • A Neuro-hormonal Circuit for Paternal Behavior Controlled by a Hypothalamic Network Oscillation

    • Stefanos Stagkourakis,
    • Kristina O. Smiley,
    • Paul Williams,
    • Sarah Kakadellis,
    • Katharina Ziegler,
    • Joanne Bakker,
    • Rosemary S.E. Brown,
    • Tibor Harkany,
    • David R. Grattan,
    • Christian Broberger
    Parenting strategies in males are determined by species-specific oscillation frequencies in hypothalamic dopamine neurons that define circulating prolactin levels and baseline activity of the parental neural circuit.

Resources

  • Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease

    • Wei-Ting Chen,
    • Ashley Lu,
    • Katleen Craessaerts,
    • Benjamin Pavie,
    • Carlo Sala Frigerio,
    • Nikky Corthout,
    • Xiaoyan Qian,
    • Jana Laláková,
    • Malte Kühnemund,
    • Iryna Voytyuk,
    • Leen Wolfs,
    • Renzo Mancuso,
    • Evgenia Salta,
    • Sriram Balusu,
    • An Snellinx,
    • Sebastian Munck,
    • Aleksandra Jurek,
    • Jose Fernandez Navarro,
    • Takaomi C. Saido,
    • Inge Huitinga,
    • Joakim Lundeberg,
    • Mark Fiers,
    • Bart De Strooper
    A combination of spatial transcriptomics and in situ sequencing on mouse and human brain demonstrates multicellular gene co-expression networks in Alzheimer’s disease, two of which are induced by accumulating amyloid plaques. A plaque-induced gene (PIG) network mainly involving micro- and astroglia and an oligodendrocyte gene (OLIG) and myelination response are identified.
  • Self-Reporting Transposons Enable Simultaneous Readout of Gene Expression and Transcription Factor Binding in Single Cells

    • Arnav Moudgil,
    • Michael N. Wilkinson,
    • Xuhua Chen,
    • June He,
    • Alexander J. Cammack,
    • Michael J. Vasek,
    • Tomás Lagunas Jr.,
    • Zongtai Qi,
    • Matthew A. Lalli,
    • Chuner Guo,
    • Samantha A. Morris,
    • Joseph D. Dougherty,
    • Robi D. Mitra
    Moudgil et al. present a single-cell method for simultaneously capturing gene expression and transcription factor binding site data from the same cells, first in cell lines and then in the mouse brain.
  • An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells

    • Ekaterina V. Vinogradova,
    • Xiaoyu Zhang,
    • David Remillard,
    • Daniel C. Lazar,
    • Radu M. Suciu,
    • Yujia Wang,
    • Giulia Bianco,
    • Yu Yamashita,
    • Vincent M. Crowley,
    • Michael A. Schafroth,
    • Minoru Yokoyama,
    • David B. Konrad,
    • Kenneth M. Lum,
    • Gabriel M. Simon,
    • Esther K. Kemper,
    • Michael R. Lazear,
    • Sifei Yin,
    • Megan M. Blewett,
    • Melissa M. Dix,
    • Nhan Nguyen,
    • Maxim N. Shokhirev,
    • Emily N. Chin,
    • Luke L. Lairson,
    • Bruno Melillo,
    • Stuart L. Schreiber,
    • Stefano Forli,
    • John R. Teijaro,
    • Benjamin F. Cravatt
    Integrated chemical proteomics and phenotypic screening furnishes a global portrait of cysteine reactivity and ligandability in primary human T cells and enables the discovery of electrophilic small molecules that suppress T cell activation and promote the degradation of immunomodulatory proteins.
  • A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions

    • Woj M. Wojtowicz,
    • Jost Vielmetter,
    • Ricardo A. Fernandes,
    • Dirk H. Siepe,
    • Catharine L. Eastman,
    • Gregory B. Chisholm,
    • Sarah Cox,
    • Heath Klock,
    • Paul W. Anderson,
    • Sarah M. Rue,
    • Jessica J. Miller,
    • Scott M. Glaser,
    • Melisa L. Bragstad,
    • Julie Vance,
    • Annie W. Lam,
    • Scott A. Lesley,
    • Kai Zinn,
    • K. Christopher Garcia
    A high-throughput protein-protein interaction screen, carried out to map human cell-surface receptor-ligand interactions between proteins belonging to the immunoglobulin domain superfamily (IgSF), begins to unravel the complex network of cell-surface interactions that allows cells to recognize and respond to one another and their dynamically changing environment.
  • Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers

    • Ayuko Hoshino,
    • Han Sang Kim,
    • Linda Bojmar,
    • Kofi Ennu Gyan,
    • Michele Cioffi,
    • Jonathan Hernandez,
    • Constantinos P. Zambirinis,
    • Gonçalo Rodrigues,
    • Henrik Molina,
    • Søren Heissel,
    • Milica Tesic Mark,
    • Loïc Steiner,
    • Alberto Benito-Martin,
    • Serena Lucotti,
    • Angela Di Giannatale,
    • Katharine Offer,
    • Miho Nakajima,
    • Caitlin Williams,
    • Laura Nogués,
    • Fanny A. Pelissier Vatter,
    • Ayako Hashimoto,
    • Alexander E. Davies,
    • Daniela Freitas,
    • Candia M. Kenific,
    • Yonathan Ararso,
    • Weston Buehring,
    • Pernille Lauritzen,
    • Yusuke Ogitani,
    • Kei Sugiura,
    • Naoko Takahashi,
    • Maša Alečković,
    • Kayleen A. Bailey,
    • Joshua S. Jolissant,
    • Huajuan Wang,
    • Ashton Harris,
    • L. Miles Schaeffer,
    • Guillermo García-Santos,
    • Zoe Posner,
    • Vinod P. Balachandran,
    • Yasmin Khakoo,
    • G. Praveen Raju,
    • Avigdor Scherz,
    • Irit Sagi,
    • Ruth Scherz-Shouval,
    • Yosef Yarden,
    • Moshe Oren,
    • Mahathi Malladi,
    • Mary Petriccione,
    • Kevin C. De Braganca,
    • Maria Donzelli,
    • Cheryl Fischer,
    • Stephanie Vitolano,
    • Geraldine P. Wright,
    • Lee Ganshaw,
    • Mariel Marrano,
    • Amina Ahmed,
    • Joe DeStefano,
    • Enrico Danzer,
    • Michael H.A. Roehrl,
    • Norman J. Lacayo,
    • Theresa C. Vincent,
    • Martin R. Weiser,
    • Mary S. Brady,
    • Paul A. Meyers,
    • Leonard H. Wexler,
    • Srikanth R. Ambati,
    • Alexander J. Chou,
    • Emily K. Slotkin,
    • Shakeel Modak,
    • Stephen S. Roberts,
    • Ellen M. Basu,
    • Daniel Diolaiti,
    • Benjamin A. Krantz,
    • Fatima Cardoso,
    • Amber L. Simpson,
    • Michael Berger,
    • Charles M. Rudin,
    • Diane M. Simeone,
    • Maneesh Jain,
    • Cyrus M. Ghajar,
    • Surinder K. Batra,
    • Ben Z. Stanger,
    • Jack Bui,
    • Kristy A. Brown,
    • Vinagolu K. Rajasekhar,
    • John H. Healey,
    • Maria de Sousa,
    • Kim Kramer,
    • Sujit Sheth,
    • Jeanine Baisch,
    • Virginia Pascual,
    • Todd E. Heaton,
    • Michael P. La Quaglia,
    • David J. Pisapia,
    • Robert Schwartz,
    • Haiying Zhang,
    • Yuan Liu,
    • Arti Shukla,
    • Laurence Blavier,
    • Yves A. DeClerck,
    • Mark LaBarge,
    • Mina J. Bissell,
    • Thomas C. Caffrey,
    • Paul M. Grandgenett,
    • Michael A. Hollingsworth,
    • Jacqueline Bromberg,
    • Bruno Costa-Silva,
    • Hector Peinado,
    • Yibin Kang,
    • Benjamin A. Garcia,
    • Eileen M. O’Reilly,
    • David Kelsen,
    • Tanya M. Trippett,
    • David R. Jones,
    • Irina R. Matei,
    • William R. Jarnagin,
    • David Lyden
    A comprehensive proteomic analysis of extracellular vesicles and particles (EVPs) from 426 human samples identifies pan-EVP markers, biomarkers for EVP isolation, for cancer detection and determining cancer type.

Correction

  • High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

    • Joep Beumer,
    • Jens Puschhof,
    • Julia Bauzá -Martinez,
    • Adriana Martínez-Silgado,
    • Rasa Elmentaite,
    • Kylie R. James,
    • Alexander Ross,
    • Delilah Hendriks,
    • Benedetta Artegiani,
    • Georg A. Busslinger,
    • Bas Ponsioen,
    • Amanda Andersson-Rolf,
    • Aurelia Saftien,
    • Charelle Boot,
    • Kai Kretzschmar,
    • Maarten H. Geurts,
    • Yotam E. Bar-Ephraim,
    • Cayetano Pleguezuelos-Manzano,
    • Yorick Post,
    • Harry Begthel,
    • Franka van der Linden,
    • Carmen Lopez-Iglesias,
    • Willine J. van de Wetering,
    • Reinier van der Linden,
    • Peter J. Peters,
    • Albert J.R. Heck,
    • Joachim Goedhart,
    • Hugo Snippert,
    • Matthias Zilbauer,
    • Sarah A. Teichmann,
    • Wei Wu,
    • Hans Clevers
    (Cell 181, 1291–1306.e1–e19; June 11, 2020)

SnapShot

  • SnapShot: FABP Functions

    • Bing Li,
    • Jiaqing Hao,
    • Jun Zeng,
    • Edward R. Sauter
    Fatty acid binding proteins (FABPs) serve as intracellular chaperones for fatty acids and other hydrophobic ligands inside cells. Recent studies have demonstrated new functions of individual members of the FABP family. This Snapshot describes the overall functions of FABPs in health and disease and highlights emerging roles of adipose FABP (A-FABP) and epidermal FABP (E-FABP) in the fields of obesity, chronic inflammation, and cancer development. To view this SnapShot, open or download the PDF.
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