Showing papers in "Cell in 2014"

TL;DR: In situ Hi-C is used to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types, identifying ∼10,000 loops that frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species.

TL;DR: In this paper, the authors describe the development and applications of Cas9 for a variety of research or translational applications while highlighting challenges as well as future directions, and highlight challenges and future directions.

TL;DR: Targeted metabolomic profiling and chemoproteomics revealed that GPX4 is an essential regulator of ferroptotic cancer cell death and sensitivity profiling in 177 cancer cell lines revealed that diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPx4-regulated ferroPTosis.

TL;DR: In high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses.

TL;DR: Compared microbiotas across >1,000 fecal samples obtained from the TwinsUK population, many microbial taxa whose abundances were influenced by host genetics were identified.

TL;DR: The genomic landscape of 496 PTCs is described and a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties is proposed, which has the potential to improve their pathological classification and better inform the management of the disease.

TL;DR: This work identifies rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%-99% knockdown with minimal off-target effects, and activators to endogenous genes via endonuclease-deficient Cas9, which enable modulation of gene expression over a ∼1,000-fold range.

TL;DR: Using mouse models with tagged mammary tumors, it is demonstrated that CTC clusters arise from oligoclonal tumor cell groupings and not from intravascular aggregation events, and though rare in the circulation, they greatly contribute to the metastatic spread of cancer.

TL;DR: The pathway of ncRNA research is described, where every established "rule" seems destined to be overturned.

TL;DR: This Review summarizes recent insights into inflammasome biology and discusses the questions that remain in the field.

TL;DR: New perspective is gained on the roles played by adipocyte in a variety of homeostatic processes and on the mechanisms used by adipocytes to communicate with other tissues and how these relationships are altered during metabolic disease and how they might be manipulated to restore metabolic health.

TL;DR: In this article, the crystal structure of the CRISPR-associated endonuclease Cas9 in complex with sgRNA and its target DNA at 2.5-A resolution was reported.

TL;DR: A combination of tissue- and lineage-specific transcription factors form the regulatory networks controlling chromatin specification in tissue-resident macrophages, and the environment is capable of shaping the chromatin landscape of transplanted bone marrow precursors, and even differentiated macrophage can be reprogrammed when transferred into a new microenvironment.

TL;DR: A scalable differentiation protocol is reported that can generate hundreds of millions of glucose-responsive β cells from hPSC in vitro that secrete human insulin into the serum of mice shortly after transplantation in a glucose-regulated manner, and transplantation of these cells ameliorates hyperglycemia in diabetic mice.

TL;DR: Mammalian aging can be delayed with genetic, dietary, and pharmacologic approaches, and it is critical to expand geroscience research directed at extending human healthspan.

TL;DR: It is shown that the short-chain fatty acids propionate and butyrate, which are generated by fermentation of soluble fiber by the gut microbiota, activate IGN via complementary mechanisms, and the regulation of IGN is necessary for the metabolic benefits associated with SCFAs and soluble fiber.

TL;DR: In vivo as well as ex vivo genome editing using adeno-associated virus, lentivirus, or particle-mediated delivery of guide RNA in neurons, immune cells, and endothelial cells is demonstrated, suggesting that Cas9 mice empower a wide range of biological and disease modeling applications.

TL;DR: It is demonstrated that exon circularization is dependent on flanking intronic complementary sequences in human introns and that alternative formation of inverted repeated Alu pairs can lead to alternative circularization, resulting in multiple circular RNA transcripts produced from a single gene.

TL;DR: It is shown that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects.

TL;DR: DNA sequence preferences for >1,000 TFs encompassing 54 different DBD classes from 131 diverse eukaryotes are determined, finding that closely related DBDs almost always have very similar DNA sequence preferences, enabling inference of motifs for ∼34% of the ∼170,000 known or predicted eUKaryotic TFs.

TL;DR: Although the inheritance of epigenetic characters can certainly occur-particularly in plants-how much is due to the environment and the extent to which it happens in humans remain unclear.

TL;DR: An integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types revealed a unified classification into 11 major subtypes, revealing several distinct cancer types found to converge into common subtypes.

TL;DR: The map uncovers significant interconnectivity between known and candidate cancer gene products, providing unbiased evidence for an expanded functional cancer landscape, while demonstrating how high-quality interactome models will help "connect the dots" of the genomic revolution.

TL;DR: The SunTag provides a versatile platform for multimerizing proteins on a target protein scaffold and is likely to have many applications in imaging and controlling biological outputs.

TL;DR: iDISCO enables facile volume imaging of immunolabeled structures in complex tissues and reveals unexpected variability in number of apoptotic neurons within individual sensory ganglia despite tight control of total number in all ganglia.

TL;DR: This work presents a genome-wide approach, based on ribosome profiling, for measuring absolute protein synthesis rates, and reveals how general principles, important both for understanding natural systems and for synthesizing new ones, emerge from quantitative analyses of protein synthesis.

TL;DR: Using a 3D organoid system, this paper reported success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression, and CHD1 loss.

TL;DR: CUBIC enables time-course expression profiling of whole adult brains with single-cell resolution and develops a whole-brain cell-nuclear counterstaining protocol and a computational image analysis pipeline that enable the visualization and quantification of neural activities induced by environmental stimulation.

TL;DR: Fiber photometry was developed and applied to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior and captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics.

TL;DR: It is found that distinct tissue environments drive divergent programs of gene expression by differentially activating a common enhancer repertoire and by inducing the expression of divergent secondary transcription factors that collaborate with PU.1 to establish tissue-specific enhancers.