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Cell Systems

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https://www.readbyqxmd.com/read/29203279/homeostatic-cell-growth-is-accomplished-mechanically-through-membrane-tension-inhibition-of-cell-wall-synthesis
#1
Enrique R Rojas, Kerwyn Casey Huang, Julie A Theriot
Feedback mechanisms are required to coordinate balanced synthesis of subcellular components during cell growth. However, these coordination mechanisms are not apparent at steady state. Here, we elucidate the interdependence of cell growth, membrane tension, and cell-wall synthesis by observing their rapid re-coordination after osmotic shocks in Gram-positive bacteria. Single-cell experiments and mathematical modeling demonstrate that mechanical forces dually regulate cell growth: while turgor pressure produces mechanical stress within the cell wall that promotes its expansion through wall synthesis, membrane tension induces growth arrest by inhibiting wall synthesis...
November 30, 2017: Cell Systems
https://www.readbyqxmd.com/read/29199021/an-integrated-systems-genetics-and-omics-toolkit-to-probe-gene-function
#2
Hao Li, Xu Wang, Daria Rukina, Qingyao Huang, Tao Lin, Vincenzo Sorrentino, Hongbo Zhang, Maroun Bou Sleiman, Danny Arends, Aaron McDaid, Peiling Luan, Naveed Ziari, Laura A Velázquez-Villegas, Karim Gariani, Zoltan Kutalik, Kristina Schoonjans, Richard A Radcliffe, Pjotr Prins, Stephan Morgenthaler, Robert W Williams, Johan Auwerx
Identifying genetic and environmental factors that impact complex traits and common diseases is a high biomedical priority. Here, we developed, validated, and implemented a series of multi-layered systems approaches, including (expression-based) phenome-wide association, transcriptome-/proteome-wide association, and (reverse-) mediation analysis, in an open-access web server (systems-genetics.org) to expedite the systems dissection of gene function. We applied these approaches to multi-omics datasets from the BXD mouse genetic reference population, and identified and validated associations between genes and clinical and molecular phenotypes, including previously unreported links between Rpl26 and body weight, and Cpt1a and lipid metabolism...
November 30, 2017: Cell Systems
https://www.readbyqxmd.com/read/29199019/widespread-rewiring-of-genetic-networks-upon-cancer-signaling-pathway-activation
#3
Maximilian Billmann, Varun Chaudhary, Mostafa F ElMaghraby, Bernd Fischer, Michael Boutros
Cellular signaling networks coordinate physiological processes in all multicellular organisms. Within networks, modules switch their function to control signaling activity in response to the cellular context. However, systematic approaches to map the interplay of such modules have been lacking. Here, we generated a context-dependent genetic interaction network of a metazoan's signaling pathway. Using Wnt signaling in Drosophila as a model, we measured >290,000 double perturbations of the pathway in a baseline state, after activation by Wnt ligand or after loss of the tumor suppressor APC...
November 27, 2017: Cell Systems
https://www.readbyqxmd.com/read/29199022/ctcf-mediated-chromatin-loops-between-promoter-and-gene-body-regulate-alternative-splicing-across-individuals
#4
Mariana Ruiz-Velasco, Manjeet Kumar, Mang Ching Lai, Pooja Bhat, Ana Belen Solis-Pinson, Alejandro Reyes, Stefan Kleinsorg, Kyung-Min Noh, Toby J Gibson, Judith B Zaugg
The CCCTC-binding factor (CTCF) is known to establish long-range DNA contacts that alter the three-dimensional architecture of chromatin, but how the presence of CTCF influences nearby gene expression is still poorly understood. Here, we analyze CTCF chromatin immunoprecipitation sequencing, RNA sequencing, and Hi-C data, together with genotypes from a healthy human cohort, and measure statistical associations between inter-individual variability in CTCF binding and alternative exon usage. We demonstrate that CTCF-mediated chromatin loops between promoters and intragenic regions are prevalent and that when exons are in physical proximity with their promoters, CTCF binding correlates with exon inclusion in spliced mRNA...
November 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/29199020/the-library-of-integrated-network-based-cellular-signatures-nih-program-system-level-cataloging-of-human-cells-response-to-perturbations
#5
REVIEW
Alexandra B Keenan, Sherry L Jenkins, Kathleen M Jagodnik, Simon Koplev, Edward He, Denis Torre, Zichen Wang, Anders B Dohlman, Moshe C Silverstein, Alexander Lachmann, Maxim V Kuleshov, Avi Ma'ayan, Vasileios Stathias, Raymond Terryn, Daniel Cooper, Michele Forlin, Amar Koleti, Dusica Vidovic, Caty Chung, Stephan C Schürer, Jouzas Vasiliauskas, Marcin Pilarczyk, Behrouz Shamsaei, Mehdi Fazel, Yan Ren, Wen Niu, Nicholas A Clark, Shana White, Naim Mahi, Lixia Zhang, Michal Kouril, John F Reichard, Siva Sivaganesan, Mario Medvedovic, Jaroslaw Meller, Rick J Koch, Marc R Birtwistle, Ravi Iyengar, Eric A Sobie, Evren U Azeloglu, Julia Kaye, Jeannette Osterloh, Kelly Haston, Jaslin Kalra, Steve Finkbiener, Jonathan Li, Pamela Milani, Miriam Adam, Renan Escalante-Chong, Karen Sachs, Alex Lenail, Divya Ramamoorthy, Ernest Fraenkel, Gavin Daigle, Uzma Hussain, Alyssa Coye, Jeffrey Rothstein, Dhruv Sareen, Loren Ornelas, Maria Banuelos, Berhan Mandefro, Ritchie Ho, Clive N Svendsen, Ryan G Lim, Jennifer Stocksdale, Malcolm S Casale, Terri G Thompson, Jie Wu, Leslie M Thompson, Victoria Dardov, Vidya Venkatraman, Andrea Matlock, Jennifer E Van Eyk, Jacob D Jaffe, Malvina Papanastasiou, Aravind Subramanian, Todd R Golub, Sean D Erickson, Mohammad Fallahi-Sichani, Marc Hafner, Nathanael S Gray, Jia-Ren Lin, Caitlin E Mills, Jeremy L Muhlich, Mario Niepel, Caroline E Shamu, Elizabeth H Williams, David Wrobel, Peter K Sorger, Laura M Heiser, Joe W Gray, James E Korkola, Gordon B Mills, Mark LaBarge, Heidi S Feiler, Mark A Dane, Elmar Bucher, Michel Nederlof, Damir Sudar, Sean Gross, David F Kilburn, Rebecca Smith, Kaylyn Devlin, Ron Margolis, Leslie Derr, Albert Lee, Ajay Pillai
The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies...
November 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/29199018/chemical-crosslinking-mass-spectrometry-analysis-of-protein-conformations-and-supercomplexes-in-heart-tissue
#6
Juan D Chavez, Chi Fung Lee, Arianne Caudal, Andrew Keller, Rong Tian, James E Bruce
While modern structural biology technologies have greatly expanded the size and type of protein complexes that can now be studied, the ability to derive large-scale structural information on proteins and complexes as they exist within tissues is practically nonexistent. Here, we demonstrate the application of crosslinking mass spectrometry to identify protein structural features and interactions in tissue samples, providing systems structural biology insight into protein complexes as they exist in the mouse heart...
November 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/29199017/linear-integration-of-erk-activity-predominates-over-persistence-detection-in-fra-1-regulation
#7
Taryn E Gillies, Michael Pargett, Marta Minguet, Alex E Davies, John G Albeck
ERK signaling regulates the expression of target genes, but it is unclear how ERK activity dynamics are interpreted. Here, we investigate this question using simultaneous, live, single-cell imaging of two ERK activity reporters and expression of Fra-1, a target gene controlling epithelial cell identity. We find that Fra-1 is expressed in proportion to the amplitude and duration of ERK activity. In contrast to previous "persistence detector" and "selective filter" models in which Fra-1 expression only occurs when ERK activity persists beyond a threshold duration, our observations demonstrate that the network regulating Fra-1 expression integrates total ERK activity and responds to it linearly...
November 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/29153840/association-of-omics-features-with-histopathology-patterns-in-lung-adenocarcinoma
#8
Kun-Hsing Yu, Gerald J Berry, Daniel L Rubin, Christopher Ré, Russ B Altman, Michael Snyder
Adenocarcinoma accounts for more than 40% of lung malignancy, and microscopic pathology evaluation is indispensable for its diagnosis. However, how histopathology findings relate to molecular abnormalities remains largely unknown. Here, we obtained H&E-stained whole-slide histopathology images, pathology reports, RNA sequencing, and proteomics data of 538 lung adenocarcinoma patients from The Cancer Genome Atlas and used these to identify molecular pathways associated with histopathology patterns. We report cell-cycle regulation and nucleotide binding pathways underpinning tumor cell dedifferentiation, and we predicted histology grade using transcriptomics and proteomics signatures (area under curve >0...
November 13, 2017: Cell Systems
https://www.readbyqxmd.com/read/29153839/asymmetry-between-activation-and-deactivation-during-a-transcriptional-pulse
#9
Lee S S Dunham, Hiroshi Momiji, Claire V Harper, Polly J Downton, Kirsty Hey, Anne McNamara, Karen Featherstone, David G Spiller, David A Rand, Bärbel Finkenstädt, Michael R H White, Julian R E Davis
Transcription in eukaryotic cells occurs in gene-specific bursts or pulses of activity. Recent studies identified a spectrum of transcriptionally active "on-states," interspersed with periods of inactivity, but these "off-states" and the process of transcriptional deactivation are poorly understood. To examine what occurs during deactivation, we investigate the dynamics of switching between variable rates. We measured live single-cell expression of luciferase reporters from human growth hormone or human prolactin promoters in a pituitary cell line...
November 13, 2017: Cell Systems
https://www.readbyqxmd.com/read/29153838/unsupervised-trajectory-analysis-of-single-cell-rna-seq-and-imaging-data-reveals-alternative-tuft-cell-origins-in-the-gut
#10
Charles A Herring, Amrita Banerjee, Eliot T McKinley, Alan J Simmons, Jie Ping, Joseph T Roland, Jeffrey L Franklin, Qi Liu, Michael J Gerdes, Robert J Coffey, Ken S Lau
Modern single-cell technologies allow multiplexed sampling of cellular states within a tissue. However, computational tools that can infer developmental cell-state transitions reproducibly from such single-cell data are lacking. Here, we introduce p-Creode, an unsupervised algorithm that produces multi-branching graphs from single-cell data, compares graphs with differing topologies, and infers a statistically robust hierarchy of cell-state transitions that define developmental trajectories. We have applied p-Creode to mass cytometry, multiplex immunofluorescence, and single-cell RNA-seq data...
November 7, 2017: Cell Systems
https://www.readbyqxmd.com/read/29128334/a-map-of-human-mitochondrial-protein-interactions-linked-to-neurodegeneration-reveals-new-mechanisms-of-redox-homeostasis-and-nf-%C3%AE%C2%BAb-signaling
#11
Ramy H Malty, Hiroyuki Aoki, Ashwani Kumar, Sadhna Phanse, Shahreen Amin, Qingzhou Zhang, Zoran Minic, Florian Goebels, Gabriel Musso, Zhuoran Wu, Hosam Abou-Tok, Michael Meyer, Viktor Deineko, Sandy Kassir, Vishaldeep Sidhu, Matthew Jessulat, Nichollas E Scott, Xuejian Xiong, James Vlasblom, Bhanu Prasad, Leonard J Foster, Tiziana Alberio, Barbara Garavaglia, Haiyuan Yu, Gary D Bader, Ken Nakamura, John Parkinson, Mohan Babu
Mitochondrial protein (MP) dysfunction has been linked to neurodegenerative disorders (NDs); however, the discovery of the molecular mechanisms underlying NDs has been impeded by the limited characterization of interactions governing MP function. Here, using mass spectrometry (MS)-based analysis of 210 affinity-purified mitochondrial (mt) fractions isolated from 27 epitope-tagged human ND-linked MPs in HEK293 cells, we report a high-confidence MP network including 1,964 interactions among 772 proteins (>90% previously unreported)...
November 7, 2017: Cell Systems
https://www.readbyqxmd.com/read/29128333/nf-%C3%AE%C2%BAb-dynamics-discriminate-between-tnf-doses-in-single-cells
#12
Qiuhong Zhang, Sanjana Gupta, David L Schipper, Gabriel J Kowalczyk, Allison E Mancini, James R Faeder, Robin E C Lee
Although cytokine-dependent dynamics of nuclear factor κB (NF-κB) are known to encode information that regulates cell fate decisions, it is unclear whether single-cell responses are switch-like or encode more information about cytokine dose. Here, we measure the dynamic subcellular localization of NF-κB in response to a range of tumor necrosis factor (TNF) stimulation conditions to determine the prevailing mechanism of single-cell dose discrimination. Using an information theory formalism that accounts for signaling dynamics and non-responsive cell subpopulations, we find that the information transmission capacity of single cells exceeds that predicted from a switch-like response...
November 7, 2017: Cell Systems
https://www.readbyqxmd.com/read/29169019/dissecting-the-ecology-of-microbes-using-a-systems-toolbox
#13
Tatyana Saleski, James Yi Tan, Xiaoxia Nina Lin
Study of simplified microbial consortia shows that nitrogen overflow by yeast is a mechanism that supports the stable co-existence of yeasts and lactic acid bacteria.
November 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/29169018/tunable-nf-%C3%AE%C2%BAb-oscillations-in-yeast
#14
Joanne M L Ho, Jacob R Mattia, Matthew R Bennett
Studies of genetic networks in situ are confounded by unknown interactions with native networks. In Zhang et al. (2017), the authors capitalize on the fact that yeast lacks the NF-κB pathway to study the human NF-κB pathway in isolation and develop a predictive model.
November 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/29169017/looking-beyond-the-stop-sign-cell-cycle-checkpoints-reconsidered
#15
Quincey A Justman
A quantitative approach that tunes DNA damage strength and observes cell-cycle kinetics in single, unperturbed cells yields a new framework for thinking about cell-cycle checkpoints.
November 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/29169016/principles-of-systems-biology-no-23
#16
(no author information available yet)
This month: protein engineering (Mootha, Chica), synthetic biology (Khalil, You, Ting Lu, Timothy K. Lu), microbial ecology and evolution (Desai), side-stepping antibiotic resistance (Chandrasekaran), and mapping microbiomes (Borisy).
November 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/29169015/reflections-on-covers
#17
EDITORIAL
H Craig Mak
No abstract text is available yet for this article.
November 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/29102611/regulatory-dynamics-determine-cell-fate-following-abrupt-antibiotic-exposure
#18
Daniel Schultz, Adam C Palmer, Roy Kishony
Bacterial resistance mechanisms must cope with transient fast-changing conditions. These systems are often repressed in the absence of the drug, and it is unclear how their regulation can provide a quick response when challenged. Here, we focus on the tet operon, which provides resistance to tetracycline through efflux pump TetA. We show that, somewhat counterintuitively, prompt expression of the TetA repressor TetR is key for cellular survival upon abrupt drug exposure. Tracking individual cells upon exposure, we find that differences in the rate of TetR elevation result in three distinct cell fates: recovery (high rate), death due to excess TetA (intermediate rate), and death from the drug (low rate)...
November 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/29102610/systematic-analysis-of-the-determinants-of-gene-expression-noise-in-embryonic-stem-cells
#19
Andre J Faure, Jörn M Schmiedel, Ben Lehner
Isogenic cells in a common environment show substantial cell-to-cell variation in gene expression, often referred to as "expression noise." Here, we use multiple single-cell RNA-sequencing datasets to identify features associated with high or low expression noise in mouse embryonic stem cells. These include the core promoter architecture of a gene, with CpG island promoters and a TATA box associated with low and high noise, respectively. High noise is also associated with "conflicting" chromatin states-the absence of transcription-associated histone modifications or the presence of repressive ones in active genes...
November 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/29102609/dash-and-recruit-mechanism-drives-membrane-curvature-recognition-by-the-small-bacterial-protein-spovm
#20
Edward Y Kim, Erin R Tyndall, Kerwyn Casey Huang, Fang Tian, Kumaran S Ramamurthi
In Bacillus subtilis, sporulation requires that the 26-amino acid protein SpoVM embeds specifically into the forespore membrane, a structure with convex curvature. How this nanometer-sized protein can detect curves on a micrometer scale is not well understood. Here, we report that SpoVM exploits a "dash-and-recruit" mechanism to preferentially accumulate on the forespore. Using time-resolved imaging and flow cytometry, we observe that SpoVM exhibits a faster adsorption rate onto membranes of higher convex curvature...
November 22, 2017: Cell Systems
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