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Cell Systems

Shai S Shen-Orr, David Furman, Brian A Kidd, Francois Hadad, Patricia Lovelace, Ying-Wen Huang, Yael Rosenberg-Hasson, Sally Mackey, Fatemeh A Gomari Grisar, Yishai Pickman, Holden T Maecker, Yueh-Hsiu Chien, Cornelia L Dekker, Joseph C Wu, Atul J Butte, Mark M Davis
Chronic inflammation, a decline in immune responsiveness, and reduced cardiovascular function are all associated with aging, but the relationships among these phenomena remain unclear. Here, we longitudinally profiled a total of 84 signaling conditions in 91 young and older adults and observed an age-related reduction in cytokine responsiveness within four immune cell lineages, most prominently T cells. The phenotype can be partially explained by elevated baseline levels of phosphorylated STAT (pSTAT) proteins and a different response capacity of naive versus memory T cell subsets to interleukin 6 (IL-6), interferon α (IFN-α), and, to a lesser extent, IL-21 and IFN-γ...
October 12, 2016: Cell Systems
William B Zhang, Drew B Sinha, William E Pittman, Erik Hvatum, Nicholas Stroustrup, Zachary Pincus
Although many genetic factors and lifestyle interventions are known to affect the mean lifespan of animal populations, the physiological variation displayed by individuals across their lifespans remains largely uncharacterized. Here, we use a custom culture apparatus to continuously monitor five aspects of aging physiology across hundreds of isolated Caenorhabditis elegans individuals kept in a constant environment from hatching until death. Aggregating these measurements into an overall estimate of senescence, we find two chief differences between longer- and shorter-lived individuals...
October 5, 2016: Cell Systems
Mauro J Muraro, Gitanjali Dharmadhikari, Dominic Grün, Nathalie Groen, Tim Dielen, Erik Jansen, Leon van Gurp, Marten A Engelse, Francoise Carlotti, Eelco J P de Koning, Alexander van Oudenaarden
To understand organ function, it is important to have an inventory of its cell types and of their corresponding marker genes. This is a particularly challenging task for human tissues like the pancreas, because reliable markers are limited. Hence, transcriptome-wide studies are typically done on pooled islets of Langerhans, obscuring contributions from rare cell types and of potential subpopulations. To overcome this challenge, we developed an automated platform that uses FACS, robotics, and the CEL-Seq2 protocol to obtain the transcriptomes of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types...
September 29, 2016: Cell Systems
Christopher M Rose, Marta Isasa, Alban Ordureau, Miguel A Prado, Sean A Beausoleil, Mark P Jedrychowski, Daniel J Finley, J Wade Harper, Steven P Gygi
System-wide quantitative analysis of ubiquitylomes has proven to be a valuable tool for elucidating targets and mechanisms of the ubiquitin-driven signaling systems, as well as gaining insights into neurodegenerative diseases and cancer. Current mass spectrometry methods for ubiquitylome detection require large amounts of starting material and rely on stochastic data collection to increase replicate analyses. We describe a method compatible with cell line and tissue samples for large-scale quantification of 5,000-9,000 ubiquitylation forms across ten samples simultaneously...
September 21, 2016: Cell Systems
Maayan Baron, Adrian Veres, Samuel L Wolock, Aubrey L Faust, Renaud Gaujoux, Amedeo Vetere, Jennifer Hyoje Ryu, Bridget K Wagner, Shai S Shen-Orr, Allon M Klein, Douglas A Melton, Itai Yanai
Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells...
September 21, 2016: Cell Systems
Jonathan M Monk, Anna Koza, Miguel A Campodonico, Daniel Machado, Jose Miguel Seoane, Bernhard O Palsson, Markus J Herrgård, Adam M Feist
Escherichia coli strains are widely used in academic research and biotechnology. New technologies for quantifying strain-specific differences and their underlying contributing factors promise greater understanding of how these differences significantly impact physiology, synthetic biology, metabolic engineering, and process design. Here, we quantified strain-specific differences in seven widely used strains of E. coli (BL21, C, Crooks, DH5a, K-12 MG1655, K-12 W3110, and W) using genomics, phenomics, transcriptomics, and genome-scale modeling...
September 21, 2016: Cell Systems
Lynn Marie Butler, Björn Mikael Hallström, Linn Fagerberg, Fredrik Pontén, Mathias Uhlén, Thomas Renné, Jacob Odeberg
Endothelial cells line blood vessels and regulate hemostasis, inflammation, and blood pressure. Proteins critical for these specialized functions tend to be predominantly expressed in endothelial cells across vascular beds. Here, we present a systems approach to identify a panel of human endothelial-enriched genes using global, body-wide transcriptomics data from 124 tissue samples from 32 organs. We identified known and unknown endothelial-enriched gene transcripts and used antibody-based profiling to confirm expression across vascular beds...
September 14, 2016: Cell Systems
Pierre M Jean Beltran, Rommel A Mathias, Ileana M Cristea
The organelles within a eukaryotic host are manipulated by viruses to support successful virus replication and spread of infection, yet the global impact of viral infection on host organelles is poorly understood. Integrating microscopy, subcellular fractionation, mass spectrometry, and functional analyses, we conducted a cell-wide study of organelles in primary fibroblasts throughout the time course of human cytomegalovirus (HCMV) infection. We used label-free and isobaric-labeling proteomics to characterize nearly 4,000 host and 100 viral proteins, then classified their specific subcellular locations over time using machine learning...
September 14, 2016: Cell Systems
Erin B Styles, Karen J Founk, Lee A Zamparo, Tina L Sing, Dogus Altintas, Cyril Ribeyre, Virginie Ribaud, Jacques Rougemont, David Mayhew, Michael Costanzo, Matej Usaj, Adrian J Verster, Elizabeth N Koch, Daniele Novarina, Marco Graf, Brian Luke, Marco Muzi-Falconi, Chad L Myers, Robi David Mitra, David Shore, Grant W Brown, Zhaolei Zhang, Charles Boone, Brenda J Andrews
A significant challenge of functional genomics is to develop methods for genome-scale acquisition and analysis of cell biological data. Here, we present an integrated method that combines genome-wide genetic perturbation of Saccharomyces cerevisiae with high-content screening to facilitate the genetic description of sub-cellular structures and compartment morphology. As proof of principle, we used a Rad52-GFP marker to examine DNA damage foci in ∼20 million single cells from ∼5,000 different mutant backgrounds in the context of selected genetic or chemical perturbations...
September 7, 2016: Cell Systems
Anthony Mathelier, Beibei Xin, Tsu-Pei Chiu, Lin Yang, Remo Rohs, Wyeth W Wasserman
Interactions of transcription factors (TFs) with DNA comprise a complex interplay between base-specific amino acid contacts and readout of DNA structure. Recent studies have highlighted the complementarity of DNA sequence and shape in modeling TF binding in vitro. Here, we have provided a comprehensive evaluation of in vivo datasets to assess the predictive power obtained by augmenting various DNA sequence-based models of TF binding sites (TFBSs) with DNA shape features (helix twist, minor groove width, propeller twist, and roll)...
August 18, 2016: Cell Systems
Joseph Rosenbluh, Johnathan Mercer, Yashaswi Shrestha, Rachel Oliver, Pablo Tamayo, John G Doench, Itay Tirosh, Federica Piccioni, Ella Hartenian, Heiko Horn, Lola Fagbami, David E Root, Jacob Jaffe, Kasper Lage, Jesse S Boehm, William C Hahn
Genome-scale expression studies and comprehensive loss-of-function genetic screens have focused almost exclusively on the highest confidence candidate genes. Here, we describe a strategy for characterizing the lower confidence candidates identified by such approaches. We interrogated 177 genes that we classified as essential for the proliferation of cancer cells exhibiting constitutive β-catenin activity and integrated data for each of the candidates, derived from orthogonal short hairpin RNA (shRNA) knockdown and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-mediated gene editing knockout screens, to yield 69 validated genes...
September 28, 2016: Cell Systems
Christoph D Rau, Chen Gao, Yibin Wang
A systems approach deconvolutes genes specific to and enriched in endothelium from whole-organ transcriptome data, with applications to other cell types and tissues.
September 28, 2016: Cell Systems
Gary D Stormo, Basab Roy
Incorporating information about DNA structure can increase the reliability of predictions of transcription factor binding sites.
September 28, 2016: Cell Systems
Elena Ledesma-Fernández, Peter H Thorpe, Robertus A M de Bruin
Styles et al. develop an optimized method that combines high-content microscopy and automated phenotypic analysis with genome-wide yeast genetics to identify genes in DNA damage repair.
September 28, 2016: Cell Systems
(no author information available yet)
Deep study of the microbiome, virome, and genetic code headline this month's Cell Systems call (Cell Systems 1, 307).
September 28, 2016: Cell Systems
(no author information available yet)
No abstract text is available yet for this article.
September 28, 2016: Cell Systems
Zhuo Gan, Liya Ding, Christoph J Burckhardt, Jason Lowery, Assaf Zaritsky, Karlyndsay Sitterley, Andressa Mota, Nancy Costigliola, Colby G Starker, Daniel F Voytas, Jessica Tytell, Robert D Goldman, Gaudenz Danuser
Increased expression of vimentin intermediate filaments (VIFs) enhances directed cell migration, but the mechanism behind VIFs' effect on motility is not understood. VIFs interact with microtubules, whose organization contributes to polarity maintenance in migrating cells. Here, we characterize the dynamic coordination of VIF and microtubule networks in wounded monolayers of retinal pigment epithelial cells. By genome editing, we fluorescently labeled endogenous vimentin and α-tubulin, and we developed computational image analysis to delineate architecture and interactions of the two networks...
September 28, 2016: Cell Systems
Simon Joost, Amit Zeisel, Tina Jacob, Xiaoyan Sun, Gioele La Manno, Peter Lönnerberg, Sten Linnarsson, Maria Kasper
The murine epidermis with its hair follicles represents an invaluable model system for tissue regeneration and stem cell research. Here we used single-cell RNA-sequencing to reveal how cellular heterogeneity of murine telogen epidermis is tuned at the transcriptional level. Unbiased clustering of 1,422 single-cell transcriptomes revealed 25 distinct populations of interfollicular and follicular epidermal cells. Our data allowed the reconstruction of gene expression programs during epidermal differentiation and along the proximal-distal axis of the hair follicle at unprecedented resolution...
September 28, 2016: Cell Systems
Tat-Ming Lo, Si Hui Chng, Wei Suong Teo, Han-Saem Cho, Matthew Wook Chang
We present a synthetic gene circuit for decoupling cell growth from metabolite production through autonomous regulation of enzymatic pathways by integrated modules that sense nutrient and substrate. The two-layer circuit allows Escherichia coli to selectively utilize target substrates in a mixed pool; channel metabolic resources to growth by delaying enzymatic conversion until nutrient depletion; and activate, terminate, and re-activate conversion upon substrate availability. We developed two versions of controller, both of which have glucose nutrient sensors but differ in their substrate-sensing modules...
August 2016: Cell Systems
Aaron N Brooks, William F Mueller, Lars M Steinmetz
A new multiomic network inference pipeline, SYGNAL, integrates patient data with mechanistically accurate transcriptional regulatory networks to predict drug combinations with synergistic anti-proliferative effects on glioblastoma multiforme.
August 2016: Cell Systems
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