Search our Database of Scientific Publications and Authors

I’m looking for a

    18866 results match your criteria Cell[Journal]

    1 OF 378

    Structure of an Intron Lariat Spliceosome from Saccharomyces cerevisiae.
    Cell 2017 Sep 14;171(1):120-132.e12. Epub 2017 Sep 14.
    Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China; Institute of Biology, Westlake Institute for Advanced Study, Westlake University, Shilongshan Road No. 18, Xihu District, Hangzhou 310064, Zhejiang Province, China. Electronic address:
    The disassembly of the intron lariat spliceosome (ILS) marks the end of a splicing cycle. Here we report a cryoelectron microscopy structure of the ILS complex from Saccharomyces cerevisiae at an average resolution of 3.5 Å. Read More

    Slp1-Emp65: A Guardian Factor that Protects Folding Polypeptides from Promiscuous Degradation.
    Cell 2017 Sep 11. Epub 2017 Sep 11.
    Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117604, Singapore; Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore. Electronic address:
    Newly synthesized proteins engage molecular chaperones that assist folding. Their progress is monitored by quality control systems that target folding errors for degradation. Paradoxically, chaperones that promote folding also direct unfolded polypeptides for degradation. Read More

    Engineering Quantitative Trait Variation for Crop Improvement by Genome Editing.
    Cell 2017 Sep 13. Epub 2017 Sep 13.
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. Electronic address:
    Major advances in crop yields are needed in the coming decades. However, plant breeding is currently limited by incremental improvements in quantitative traits that often rely on laborious selection of rare naturally occurring mutations in gene-regulatory regions. Here, we demonstrate that CRISPR/Cas9 genome editing of promoters generates diverse cis-regulatory alleles that provide beneficial quantitative variation for breeding. Read More

    Mitochondrial Priming by CD28.
    Cell 2017 Sep 1. Epub 2017 Sep 1.
    Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany. Electronic address:
    T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand. Read More

    Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch.
    Cell 2017 Sep 7;171(1):217-228.e13. Epub 2017 Sep 7.
    Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:
    Mammals have evolved neurophysiologic reflexes, such as coughing and scratching, to expel invading pathogens and noxious environmental stimuli. It is well established that these responses are also associated with chronic inflammatory diseases, including asthma and atopic dermatitis. However, the mechanisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Read More

    In Situ Architecture and Cellular Interactions of PolyQ Inclusions.
    Cell 2017 Sep 7;171(1):179-187.e10. Epub 2017 Sep 7.
    Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
    Expression of many disease-related aggregation-prone proteins results in cytotoxicity and the formation of large intracellular inclusion bodies. To gain insight into the role of inclusions in pathology and the in situ structure of protein aggregates inside cells, we employ advanced cryo-electron tomography methods to analyze the structure of inclusions formed by polyglutamine (polyQ)-expanded huntingtin exon 1 within their intact cellular context. In primary mouse neurons and immortalized human cells, polyQ inclusions consist of amyloid-like fibrils that interact with cellular endomembranes, particularly of the endoplasmic reticulum (ER). Read More

    Artists Create Puzzles, Scientists Solve Them.
    Cell 2017 Sep 6;171(1):5-9. Epub 2017 Sep 6.
    Chair, Lasker Awards Jury; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:
    The Spanish artist Diego Velázquez created a puzzle-painting 360 years ago that to this day remains unsolved, but still mystifies and intrigues. Unlike artists who get their thrills by creating puzzles that stimulate the imagination, scientists get their kicks by solving puzzles that advance biomedical research. Read More

    A Prize for Cancer Prevention.
    Cell 2017 Sep 6;171(1):14-17. Epub 2017 Sep 6.
    Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address:
    This year's Lasker-DeBakey Prize for Clinical Research to Douglas Lowy and John Schiller celebrates the science behind one of the greatest advances in the history of cancer research: the development of vaccines that prevent infection and thus prevent tumor induction by pathogenic strains of human papilloma virus (HPV). Read More

    Two Basic Scientists Walk into a Translational Space.
    • Authors:
    Cell 2017 Sep 6;171(1):23-27. Epub 2017 Sep 6.
    When John Schiller first joined Douglas Lowy's lab at the National Cancer Institute of the NIH, he could have not predicted that their common interest in the molecular biology of oncogenes would set them in path for discoveries that ultimately enabled the development of a vaccine for the human papillomavirus, which causes the majority of cervical cancers worldwide. John and Doug, the recipients of the 2017 Lasker-DeBakey Clinical Award, have joined Cell editor João Monteiro in a Conversation about science, public health, and the joys and challenges of being basic scientists in a translational space. Annotated excerpts from this conversation are presented below. Read More

    TOR, the Gateway to Cellular Metabolism, Cell Growth, and Disease.
    Cell 2017 Sep 6;171(1):10-13. Epub 2017 Sep 6.
    Meyer Cancer Center and Department of Pharmacology, Weill Cornell Medicine, 413 East 69(th) Street, New York, NY 10021, USA. Electronic address:
    Michael N. Hall is this year's recipient of the Lasker Basic Medical Research Award for the identification of the target of rapamycin, TOR. TOR is a master regulator of the cell's growth and metabolic state, and its dysregulation contributes to a variety of diseases, including diabetes, obesity, neurodegenerative disorders, aging, and cancer, making the TOR pathway an attractive therapeutic target. Read More

    SnapShot: Connexins and Disease.
    Cell 2017 Sep;170(6):1260-1260.e1
    Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
    The connexin family of membrane proteins enable gap junction formation and homeostasis, supporting communication between adjacent cells. This SnapShot highlights mutations in different connexins associated with human pathologies and how they affect gap junction function. Read More

    Lis1 Has Two Opposing Modes of Regulating Cytoplasmic Dynein.
    Cell 2017 Sep;170(6):1197-1208.e12
    Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address:
    Regulation is central to the functional versatility of cytoplasmic dynein, a motor involved in intracellular transport, cell division, and neurodevelopment. Previous work established that Lis1, a conserved regulator of dynein, binds to its motor domain and induces a tight microtubule-binding state in dynein. The work we present here-a combination of biochemistry, single-molecule assays, and cryoelectron microscopy-led to the surprising discovery that Lis1 has two opposing modes of regulating dynein, being capable of inducing both low and high affinity for the microtubule. Read More

    Combinatorial Signal Perception in the BMP Pathway.
    Cell 2017 Sep;170(6):1184-1196.e24
    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute and Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address:
    The bone morphogenetic protein (BMP) signaling pathway comprises multiple ligands and receptors that interact promiscuously with one another and typically appear in combinations. This feature is often explained in terms of redundancy and regulatory flexibility, but it has remained unclear what signal-processing capabilities it provides. Here, we show that the BMP pathway processes multi-ligand inputs using a specific repertoire of computations, including ratiometric sensing, balance detection, and imbalance detection. Read More

    HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis.
    Cell 2017 Sep;170(6):1164-1174.e6
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
    Although most cervical human papillomavirus type 16 (HPV16) infections become undetectable within 1-2 years, persistent HPV16 causes half of all cervical cancers. We used a novel HPV whole-genome sequencing technique to evaluate an exceptionally large collection of 5,570 HPV16-infected case-control samples to determine whether viral genetic variation influences risk of cervical precancer and cancer. We observed thousands of unique HPV16 genomes; very few women shared the identical HPV16 sequence, which should stimulate a careful re-evaluation of the clinical implications of HPV mutation rates, transmission, clearance, and persistence. Read More

    Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6.
    Cell 2017 Sep;170(6):1149-1163.e12
    Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
    The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissues, are markers of mesenchymal cells in the adult lung. Lgr6(+) cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia and promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation. Read More

    Distinct Mesenchymal Lineages and Niches Promote Epithelial Self-Renewal and Myofibrogenesis in the Lung.
    Cell 2017 Sep;170(6):1134-1148.e10
    Department of Medicine, Division of Pediatric Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Center for Pulmonary Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:
    The lung is an architecturally complex organ comprising a heterogeneous mixture of various epithelial and mesenchymal lineages. We use single-cell RNA sequencing and signaling lineage reporters to generate a spatial and transcriptional map of the lung mesenchyme. We find that each mesenchymal lineage has a distinct spatial address and transcriptional profile leading to unique niche regulatory functions. Read More

    Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy.
    Cell 2017 Sep;170(6):1109-1119.e10
    Melanoma Institute Australia, The University of Sydney and Royal North Shore and Mater Hospitals, Sydney, NSW, Australia.
    Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. Read More

    NF-κB c-Rel Is Crucial for the Regulatory T Cell Immune Checkpoint in Cancer.
    Cell 2017 Sep;170(6):1096-1108.e13
    Department of Microbiology & Immunology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA. Electronic address:
    Regulatory T cells (Tregs) play a pivotal role in the inhibition of anti-tumor immune responses. Understanding the mechanisms governing Treg homeostasis may therefore be important for development of effective tumor immunotherapy. We have recently demonstrated a key role for the canonical nuclear factor κB (NF-κB) subunits, p65 and c-Rel, in Treg identity and function. Read More

    Putting p53 in Context.
    Cell 2017 Sep;170(6):1062-1078
    Department of Cancer Biology and Genetics, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute, New York, NY 10065, USA. Electronic address:
    TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. Read More

    Eukaryotic Sexual Reproduction Evoked "with a Little Help from My Friends".
    Cell 2017 Sep;170(6):1059-1061
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:
    Bacteria and eukaryotes interact in many ways-from the microbiome that educates the mammalian immune system and enhances nutrition to relationships that are commensal, symbiotic, or parasitic. Now in an unexpected twist, King and colleagues have expanded the repertoire of prokaryotic influence over eukaryotic physiology to include mating. Read More

    Crowd Control: E7 Conservation Is the Key to Cancer.
    Cell 2017 Sep;170(6):1057-1059
    Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA. Electronic address:
    Several human papillomavirus type 16 (HPV16) oncoproteins contribute to cellular transformation in vitro. In this issue of Cell, Mirabello and colleagues use high-throughput sequencing data to assess the diversity of HPV16 isolates from human patients. These data suggest that the E7 oncoprotein is the fundamental contributor to in vivo carcinogenesis. Read More

    Converting Cold into Hot Tumors by Combining Immunotherapies.
    Cell 2017 Sep;170(6):1055-1056
    The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, the Netherlands. Electronic address:
    In a small phase Ib study in this issue of Cell, Ribas et al. report that the combination of intralesional injection of a modified human herpes simplex virus and systemic anti-PD-1 treatment resulted in a 62% response rate in patients with metastatic melanoma, accompanied by enhanced T cell infiltration in virus-injected lesions. Read More

    Barbara McClintock's Final Years as Nobelist and Mentor: A Memoir.
    Cell 2017 Sep;170(6):1049-1054
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. Electronic address:
    September 2, 2017, marks the 25(th) year after the passing of Dr. Barbara McClintock, geneticist and recipient of the 1983 Nobel Prize in Physiology or Medicine for her discovery of transposable elements in maize. This memoir focuses on the last years of her life-after the prize-and includes personal recollections of how she mentored young scientists and inspired the age of genetics, epigenetics, and genomics. Read More

    Dynamic Control of X Chromosome Conformation and Repression by a Histone H4K20 Demethylase.
    Cell 2017 Sep 31;171(1):85-102.e23. Epub 2017 Aug 31.
    Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3204, USA. Electronic address:
    Chromatin modification and higher-order chromosome structure play key roles in gene regulation, but their functional interplay in controlling gene expression is elusive. We have discovered the machinery and mechanism underlying the dynamic enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during C. elegans dosage compensation and demonstrated H4K20me1's pivotal role in regulating higher-order chromosome structure and X-chromosome-wide gene expression. Read More

    Load Adaptation of Lamellipodial Actin Networks.
    Cell 2017 Sep 31;171(1):188-200.e16. Epub 2017 Aug 31.
    Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria. Electronic address:
    Actin filaments polymerizing against membranes power endocytosis, vesicular traffic, and cell motility. In vitro reconstitution studies suggest that the structure and the dynamics of actin networks respond to mechanical forces. We demonstrate that lamellipodial actin of migrating cells responds to mechanical load when membrane tension is modulated. Read More

    Mating in the Closest Living Relatives of Animals Is Induced by a Bacterial Chondroitinase.
    Cell 2017 Sep 31;170(6):1175-1183.e11. Epub 2017 Aug 31.
    Howard Hughes Medical Institute, and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address:
    We serendipitously discovered that the marine bacterium Vibrio fischeri induces sexual reproduction in one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. Although bacteria influence everything from nutrition and metabolism to cell biology and development in eukaryotes, bacterial regulation of eukaryotic mating was unexpected. Here, we show that a single V. Read More

    Architecture of Human Mitochondrial Respiratory Megacomplex I2III2IV2.
    Cell 2017 Sep 24;170(6):1247-1257.e12. Epub 2017 Aug 24.
    Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, 100084 Beijing, China. Electronic address:
    The respiratory megacomplex represents the highest-order assembly of respiratory chain complexes, and it allows mitochondria to respond to energy-requiring conditions. To understand its architecture, we examined the human respiratory chain megacomplex-I2III2IV2 (MCI2III2IV2) with 140 subunits and a subset of associated cofactors using cryo-electron microscopy. The MCI2III2IV2 forms a circular structure with the dimeric CIII located in the center, where it is surrounded by two copies each of CI and CIV. Read More

    Cancer-Specific Retargeting of BAF Complexes by a Prion-like Domain.
    Cell 2017 Sep 24;171(1):163-178.e19. Epub 2017 Aug 24.
    Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Electronic address:
    Alterations in transcriptional regulators can orchestrate oncogenic gene expression programs in cancer. Here, we show that the BRG1/BRM-associated factor (BAF) chromatin remodeling complex, which is mutated in over 20% of human tumors, interacts with EWSR1, a member of a family of proteins with prion-like domains (PrLD) that are frequent partners in oncogenic fusions with transcription factors. In Ewing sarcoma, we find that the BAF complex is recruited by the EWS-FLI1 fusion protein to tumor-specific enhancers and contributes to target gene activation. Read More

    Regulatory Innate Lymphoid Cells Control Innate Intestinal Inflammation.
    Cell 2017 Sep 24;171(1):201-216.e18. Epub 2017 Aug 24.
    CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, China; University of Chinese Academy of Sciences, 100049 Beijing, China. Electronic address:
    An emerging family of innate lymphoid cells (termed ILCs) has an essential role in the initiation and regulation of inflammation. However, it is still unclear how ILCs are regulated in the duration of intestinal inflammation. Here, we identify a regulatory subpopulation of ILCs (called ILCregs) that exists in the gut and harbors a unique gene identity that is distinct from that of ILCs or regulatory T cells (Tregs). Read More

    A Broad-Spectrum Inhibitor of CRISPR-Cas9.
    Cell 2017 Sep 24;170(6):1224-1233.e15. Epub 2017 Aug 24.
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address:
    CRISPR-Cas9 proteins function within bacterial immune systems to target and destroy invasive DNA and have been harnessed as a robust technology for genome editing. Small bacteriophage-encoded anti-CRISPR proteins (Acrs) can inactivate Cas9, providing an efficient off switch for Cas9-based applications. Here, we show that two Acrs, AcrIIC1 and AcrIIC3, inhibit Cas9 by distinct strategies. Read More

    A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy.
    Cell 2017 Aug;170(5):973-985.e10
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA; Department of Immunology, University of Washington, Seattle, WA 98195, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA; MRC Laboratory of Molecular Biology, Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge CB2 OQH, UK. Electronic address:
    Mycobacterium leprae causes leprosy and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from direct interaction of the M. leprae-specific phenolic glycolipid 1 (PGL-1) with myelinating glia and their subsequent infection. Read More

    DNA Cross-Bridging Shapes a Single Nucleus from a Set of Mitotic Chromosomes.
    Cell 2017 Aug;170(5):956-972.e23
    Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), 1030 Vienna, Austria. Electronic address:
    Eukaryotic cells store their chromosomes in a single nucleus. This is important to maintain genomic integrity, as chromosomes packaged into separate nuclei (micronuclei) are prone to massive DNA damage. During mitosis, higher eukaryotes disassemble their nucleus and release individualized chromosomes for segregation. Read More

    Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient.
    Cell 2017 Aug;170(5):927-938.e20
    Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. Electronic address:
    We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8(+) and CD4(+) T cells and exhibited oligoclonal expansion of specific T cell subsets. We also detected CD8(+) T cell reactivity against predicted neoepitopes after isolation of cells from a blood sample taken almost 3 years after the tumors were resected. Read More

    Clonal Evolution of Autoreactive Germinal Centers.
    Cell 2017 Aug;170(5):913-926.e19
    Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
    Germinal centers (GCs) are the primary sites of clonal B cell expansion and affinity maturation, directing the production of high-affinity antibodies. This response is a central driver of pathogenesis in autoimmune diseases, such as systemic lupus erythematosus (SLE), but the natural history of autoreactive GCs remains unclear. Here, we present a novel mouse model where the presence of a single autoreactive B cell clone drives the TLR7-dependent activation, expansion, and differentiation of other autoreactive B cells in spontaneous GCs. Read More

    High-Definition Medicine.
    Cell 2017 Aug;170(5):828-843
    The Scripps Translational Science Institute, La Jolla, CA 92037, USA; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
    The foundation for a new era of data-driven medicine has been set by recent technological advances that enable the assessment and management of human health at an unprecedented level of resolution-what we refer to as high-definition medicine. Our ability to assess human health in high definition is enabled, in part, by advances in DNA sequencing, physiological and environmental monitoring, advanced imaging, and behavioral tracking. Our ability to understand and act upon these observations at equally high precision is driven by advances in genome editing, cellular reprogramming, tissue engineering, and information technologies, especially artificial intelligence. Read More

    Cancer Evolution Constrained by the Immune Microenvironment.
    Cell 2017 08;170(5):825-827
    Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6BT, UK; Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK. Electronic address:
    Tumor development is a Darwinian evolutionary process, involving the interplay between cancer subclones and the local immune microenvironment. These complex interactions are highlighted in this issue of Cell by the results from Jiménez-Sánchez et al. of a deep analysis of one patient with advanced serous carcinoma of the ovary. Read More

    Reprogramming Enhancers to Drive Metastasis.
    Cell 2017 08;170(5):823-825
    The Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA; Massachusetts General Hospital Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA. Electronic address:
    Acquired molecular changes can promote the spreading of primary tumor cells to distant tissues. In this issue of Cell, Roe et al. show that metastatic progression of pancreatic cancer involves large-scale enhancer reprogramming by Foxa1, which activates transcriptional program specifying early endodermal stem cells. Read More

    The Tropism of Pleiotrophin: Orchestrating Glioma Brain Invasion.
    Cell 2017 08;170(5):821-822
    Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:
    The lateral ventricle (LV) is a preferential location for brain tumor spread; however, the instructive cues responsible for this unique tropism were previously unknown. In this issue, Qin et al. elucidate the underlying mechanism, demonstrating that LV-neural progenitors secrete a pleiotrophin (PTN)-containing complex, which attracts glioma cells through ROCK/Rho activation. Read More

    SnapShot: Cellular Senescence in Pathophysiology.
    Cell 2017 Aug;170(5):1044-1044.e1
    INSERM, U993, 75015 Paris, France; Equipe Labellisée Fondation ARC pour la recherche sur le cancer, 94803 Villejuif, France; Institut Pasteur, Molecular and Cellular Biology of Cellular Senescence and Age-Related Pathologies Group, Nuclear Organization and Oncogenesis Unit, Department of Cell Biology and Infection, 75015 Paris, France.
    Cellular senescence is a fundamental cell fate, important both in physiological and pathophysiological processes. This SnapShot focuses on the role of cellular senescence in health, disease, and aging. Read More

    In Situ Capture of Chromatin Interactions by Biotinylated dCas9.
    Cell 2017 Aug;170(5):1028-1043.e19
    Children's Medical Center Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:
    Cis-regulatory elements (CREs) are commonly recognized by correlative chromatin features, yet the molecular composition of the vast majority of CREs in chromatin remains unknown. Here, we describe a CRISPR affinity purification in situ of regulatory elements (CAPTURE) approach to unbiasedly identify locus-specific chromatin-regulating protein complexes and long-range DNA interactions. Using an in vivo biotinylated nuclease-deficient Cas9 protein and sequence-specific guide RNAs, we show high-resolution and selective isolation of chromatin interactions at a single-copy genomic locus. Read More

    Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking.
    Cell 2017 Aug 17;170(5):1013-1027.e14. Epub 2017 Aug 17.
    HHMI, Stanford University, Stanford, CA, 94305, USA; Department of Psychiatry, Stanford University, Stanford, CA, 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA. Electronic address:
    Reward-seeking behavior is fundamental to survival, but suppression of this behavior can be essential as well, even for rewards of high value. In humans and rodents, the medial prefrontal cortex (mPFC) has been implicated in suppressing reward seeking; however, despite vital significance in health and disease, the neural circuitry through which mPFC regulates reward seeking remains incompletely understood. Here, we show that a specific subset of superficial mPFC projections to a subfield of nucleus accumbens (NAc) neurons naturally encodes the decision to initiate or suppress reward seeking when faced with risk of punishment. Read More

    1 OF 378