Intestinal Dysmotility Syndromes following Systemic Infection by Flaviviruses
Publication date: Available online 4 October 2018Source: CellAuthor(s): James P. White, Shanshan Xiong, Nicole P. Malvin, William Khoury-Hanold, Robert O. Heuckeroth, Thaddeus S. Stappenbeck, Michael S. DiamondSummaryAlthough chronic gastrointestinal dysmotility syndromes are a common worldwide health problem, underlying causes for these disorders are poorly understood. We show that flavivirus infection of enteric neurons leads to acute neuronal injury and cell death, inflammation, bowel dilation, and slowing of intestinal transit in mice. Flavivirus-primed CD8+ T cells promote these phenotypes, as their absence dimin...
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

An Endothelial-to-Adipocyte Extracellular Vesicle Axis Governed by Metabolic State
Publication date: Available online 4 October 2018Source: CellAuthor(s): Clair Crewe, Nolwenn Joffin, Joseph M. Rutkowski, Min Kim, Fang Zhang, Dwight A. Towler, Ruth Gordillo, Philipp E. SchererSummaryWe have uncovered the existence of extracellular vesicle (EV)-mediated signaling between cell types within the adipose tissue (AT) proper. This phenomenon became evident in our attempts at generating an adipocyte-specific knockout of caveolin 1 (cav1) protein. Although we effectively ablated the CAV1 gene in adipocytes, cav1 protein remained abundant. With the use of newly generated mouse models, we show that neighboring endo...
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

The Human Transcription Factors
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): Samuel A. Lambert, Arttu Jolma, Laura F. Campitelli, Pratyush K. Das, Yimeng Yin, Mihai Albu, Xiaoting Chen, Jussi Taipale, Timothy R. Hughes, Matthew T. Weirauch (Source: Cell)
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

Interred with Their DNA
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): Stacie Dodgson (Source: Cell)
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

Addressing Diversity and Inclusion in Human Genetics Research
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): (Source: Cell)
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

Simultaneous Viral Exposure and Protection from Neanderthal Introgression
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): Emilia Huerta-Sánchez, Fergal P. CaseyIn this issue, Enard and Petrov present intriguing results on the possibility of genetic traces left behind in our genomes from adaptation to past viral epidemics that may have been initiated by interaction with Neanderthal archaic hominins. The work highlights how powerful infectious agents can act as a selective force to shape our genetic makeup. (Source: Cell)
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

Aster: A New Star in Cholesterol Trafficking
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): Vassily I. Kutyavin, Ajay ChawlaLife evolved in an aqueous environment, necessitating the evolution of carrier proteins to shuttle lipophilic molecules within and between cells. Sandhu et. al. (2018) report the discovery of a long-sought-after cholesterol carrier protein, named Aster, which transports cholesterol from the plasma membrane to the endoplasmic reticulum. (Source: Cell)
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

Exposing a Virus Hiding in the Animal Facility
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): Colin R. ParrishRoediger et al. (2018) demonstrate that a kidney disease characterized by apparently spontaneous nephropathy that had been recognized in laboratory mice for many years is caused by a newly recognized virus named the mouse kidney parvovirus (MKPV). That virus appears to be widespread in mouse colonies as it is not detected by current diagnostic tools, and its recognition presents new opportunities for understanding the pathology of tubulointerstitial fibrosis. (Source: Cell)
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

Bacterial Siderophores Promote Animal Host Iron Acquisition and Growth
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): Dennis H. KimSiderophores are small molecules produced by bacteria that bind ferric iron in the surrounding environment with extraordinary affinity. A new study provides evidence that a simple animal host, Caenorhabditis elegans, co-opts siderophores to promote its own iron acquisition and growth. (Source: Cell)
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): Miguel F. Sanmamed, Lieping ChenHarnessing an antitumor immune response has been a fundamental strategy in cancer immunotherapy. For over a century, efforts have primarily focused on amplifying immune activation mechanisms that are employed by humans to eliminate invaders such as viruses and bacteria. This “immune enhancement” strategy often results in rare objective responses and frequent immune-related adverse events (irAEs). However, in the last decade, cancer immunotherapies targeting the B7-H1/PD-1 pathway (anti-PD therapy), have a...
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

The Cellular and Molecular Basis for Planarian Regeneration
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): Peter W. ReddienRegeneration is one of the great mysteries of biology. Planarians are flatworms capable of dramatic feats of regeneration, which have been studied for over 2 centuries. Recent findings identify key cellular and molecular principles underlying these feats. A stem cell population (neoblasts) generates new cells and is comprised of pluripotent stem cells (cNeoblasts) and fate-specified cells (specialized neoblasts). Positional information is constitutively active and harbored primarily in muscle, where it acts to guide stem cell-mediat...
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations, Patterns of Viral Infections, and Chinese Population History
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): Siyang Liu, Shujia Huang, Fang Chen, Lijian Zhao, Yuying Yuan, Stephen Starko Francis, Lin Fang, Zilong Li, Long Lin, Rong Liu, Yong Zhang, Huixin Xu, Shengkang Li, Yuwen Zhou, Robert W. Davies, Qiang Liu, Robin G. Walters, Kuang Lin, Jia Ju, Thorfinn KorneliussenSummaryWe analyze whole-genome sequencing data from 141,431 Chinese women generated for non-invasive prenatal testing (NIPT). We use these data to characterize the population genetic structure and to investigate genetic associations with maternal and infectious traits. We show that the pre...
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

Immune Checkpoint Inhibition Overcomes ADCP-Induced Immunosuppression by Macrophages
We report here an unexpected finding that macrophages after ADCP inhibit NK cell-mediated ADCC and T cell-mediated cytotoxicity in breast cancers and lymphomas. Mechanistically, AIM2 is recruited to the phagosomes by FcγR signaling following ADCP and activated by sensing the phagocytosed tumor DNAs through the disrupted phagosomal membrane, which subsequently upregulates PD-L1 and IDO and causes immunosuppression. Combined treatment with anti-HER2 antibody and inhibitors of PD-L1 and IDO enhances anti-tumor immunity and anti-HER2 therapeutic efficacy in mouse models. Furthermore, neoadjuvant trastuzumab the...
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

SnapShot: RNA Structure Probing Technologies
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): Paul D. Carlson, Molly E. Evans, Angela M Yu, Eric J. Strobel, Julius B. LucksChemical probing coupled to high-throughput sequencing offers a flexible approach to uncover many aspects of RNA structure relevant to its cellular function. With a wide variety of chemical probes available that each report on different features of RNA molecules, a broad toolkit exists for investigating in vivo and in vitro RNA structure and interactions with other molecules. (Source: Cell)
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

Evidence that RNA Viruses Drove Adaptive Introgression between Neanderthals and Modern Humans
Publication date: 4 October 2018Source: Cell, Volume 175, Issue 2Author(s): David Enard, Dmitri A. PetrovSummaryNeanderthals and modern humans interbred at least twice in the past 100,000 years. While there is evidence that most introgressed DNA segments from Neanderthals to modern humans were removed by purifying selection, less is known about the adaptive nature of introgressed sequences that were retained. We hypothesized that interbreeding between Neanderthals and modern humans led to (1) the exposure of each species to novel viruses and (2) the exchange of adaptive alleles that provided resistance against these viruse...
Source: Cell - October 5, 2018 Category: Cytology Source Type: research

A Map-like Micro-Organization of Grid Cells in the Medial Entorhinal Cortex
Publication date: Available online 27 September 2018Source: CellAuthor(s): Yi Gu, Sam Lewallen, Amina A. Kinkhabwala, Cristina Domnisoru, Kijung Yoon, Jeffrey L. Gauthier, Ila R. Fiete, David W. TankSummaryHow the topography of neural circuits relates to their function remains unclear. Although topographic maps exist for sensory and motor variables, they are rarely observed for cognitive variables. Using calcium imaging during virtual navigation, we investigated the relationship between the anatomical organization and functional properties of grid cells, which represent a cognitive code for location during navigation. We f...
Source: Cell - October 4, 2018 Category: Cytology Source Type: research

The Mevalonate Pathway Is a Druggable Target for Vaccine Adjuvant Discovery
Publication date: Available online 27 September 2018Source: CellAuthor(s): Yun Xia, Yonghua Xie, Zhengsen Yu, Hongying Xiao, Guimei Jiang, Xiaoying Zhou, Yunyun Yang, Xin Li, Meng Zhao, Liping Li, Mingke Zheng, Shuai Han, Zhaoyun Zong, Xianbin Meng, Haiteng Deng, Huahu Ye, Yunzhi Fa, Haitao Wu, Eric Oldfield, Xiaoyu HuSummaryMotivated by the clinical observation that interruption of the mevalonate pathway stimulates immune responses, we hypothesized that this pathway may function as a druggable target for vaccine adjuvant discovery. We found that lipophilic statin drugs and rationally designed bisphosphonates that target t...
Source: Cell - October 4, 2018 Category: Cytology Source Type: research

Cyclic-Nucleotide- and HCN-Channel-Mediated Phototransduction in Intrinsically Photosensitive Retinal Ganglion Cells
We report here that, surprisingly, mouse M4-ipRGCs rely on a different and hitherto undescribed melanopsin-driven, ciliary phototransduction mechanism involving cyclic nucleotide as the second messenger and HCN channels rather than CNG channels as the ion channel for phototransduction. Even more surprisingly, within an individual mouse M2-ipRGC, this HCN-channel-dependent, ciliary phototransduction pathway operates in parallel with the TRPC6,7-dependent rhabdomeric pathway. These findings reveal a complex heterogeneity in phototransduction among ipRGCs and, more importantly, break a general dogma about segregation of the t...
Source: Cell - October 4, 2018 Category: Cytology Source Type: research

Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease
Publication date: Available online 27 September 2018Source: CellAuthor(s): James Kinchen, Hannah H. Chen, Kaushal Parikh, Agne Antanaviciute, Marta Jagielowicz, David Fawkner-Corbett, Neil Ashley, Laura Cubitt, Esther Mellado-Gomez, Moustafa Attar, Eshita Sharma, Quin Wills, Rory Bowden, Felix C. Richter, David Ahern, Kamal D. Puri, Jill Henault, Francois Gervais, Hashem Koohy, Alison SimmonsSummaryIntestinal mesenchymal cells play essential roles in epithelial homeostasis, matrix remodeling, immunity, and inflammation. But the extent of heterogeneity within the colonic mesenchyme in these processes remains unknown. Using ...
Source: Cell - October 4, 2018 Category: Cytology Source Type: research

Spatial Reconstruction of Single Enterocytes Uncovers Broad Zonation along the Intestinal Villus Axis
Publication date: Available online 27 September 2018Source: CellAuthor(s): Andreas E. Moor, Yotam Harnik, Shani Ben-Moshe, Efi E. Massasa, Milena Rozenberg, Raya Eilam, Keren Bahar Halpern, Shalev ItzkovitzSummaryThe intestinal epithelium is a highly structured tissue composed of repeating crypt-villus units. Enterocytes perform the diverse tasks of absorbing a wide range of nutrients while protecting the body from the harsh bacterium-rich environment. It is unknown whether these tasks are spatially zonated along the villus axis. Here, we extracted a large panel of landmark genes characterized by transcriptomics of laser c...
Source: Cell - October 4, 2018 Category: Cytology Source Type: research

NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation
Publication date: Available online 27 September 2018Source: CellAuthor(s): Xavier Lahaye, Matteo Gentili, Aymeric Silvin, Cécile Conrad, Léa Picard, Mabel Jouve, Elina Zueva, Mathieu Maurin, Francesca Nadalin, Gavin J. Knott, Baoyu Zhao, Fenglei Du, Marlène Rio, Jeanne Amiel, Archa H. Fox, Pingwei Li, Lucie Etienne, Charles S. Bond, Laurence Colleaux, Nicolas ManelSummaryDetection of viruses by innate immune sensors induces protective antiviral immunity. The viral DNA sensor cyclic GMP-AMP synthase (cGAS) is necessary for detection of HIV by human dendritic cells and macrophages. However, synthesis of ...
Source: Cell - October 4, 2018 Category: Cytology Source Type: research

Protein AMPylation by an Evolutionarily Conserved Pseudokinase
Publication date: Available online 27 September 2018Source: CellAuthor(s): Anju Sreelatha, Samantha S. Yee, Victor A. Lopez, Brenden C. Park, Lisa N. Kinch, Sylwia Pilch, Kelly A. Servage, Junmei Zhang, Jenny Jiou, Monika Karasiewicz-Urbańska, Małgorzata Łobocka, Nick V. Grishin, Kim Orth, Roza Kucharczyk, Krzysztof Pawłowski, Diana R. Tomchick, Vincent S. TagliabracciSummaryApproximately 10% of human protein kinases are believed to be inactive and named pseudokinases because they lack residues required for catalysis. Here, we show that the highly conserved pseudokinase selenoprotein-O (SelO) transfers AMP from ATP to ...
Source: Cell - October 4, 2018 Category: Cytology Source Type: research

RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses
Publication date: Available online 27 September 2018Source: CellAuthor(s): Todd Bradley, Dimitra Peppa, Isabela Pedroza-Pacheco, Dapeng Li, Derek W. Cain, Ricardo Henao, Vaishnavi Venkat, Bhavna Hora, Yue Chen, Nathan A. Vandergrift, R. Glenn Overman, R. Whitney Edwards, Chris W. Woods, Georgia D. Tomaras, Guido Ferrari, Geoffrey S. Ginsburg, Mark Connors, Myron S. Cohen, M. Anthony Moody, Persephone BorrowSummaryHIV-1 broadly neutralizing antibodies (bnAbs) are difficult to induce with vaccines but are generated in ∼50% of HIV-1-infected individuals. Understanding the molecular mechanisms of host control of bnAb induc...
Source: Cell - October 4, 2018 Category: Cytology Source Type: research

LC3-Associated Phagocytosis in Myeloid Cells Promotes Tumor Immune Tolerance
Publication date: Available online 20 September 2018Source: CellAuthor(s): Larissa D. Cunha, Mao Yang, Robert Carter, Clifford Guy, Lacie Harris, Jeremy C. Crawford, Giovanni Quarato, Emilio Boada-Romero, Halime Kalkavan, Michael D.L. Johnson, Sivaraman Natarajan, Meghan E. Turnis, David Finkelstein, Joseph T. Opferman, Charles Gawad, Douglas R. GreenSummaryTargeting autophagy in cancer cells and in the tumor microenvironment are current goals of cancer therapy. However, components of canonical autophagy play roles in other biological processes, adding complexity to this goal. One such alternative function of autophagy pro...
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Integration of Parallel Opposing Memories Underlies Memory Extinction
Publication date: Available online 20 September 2018Source: CellAuthor(s): Johannes Felsenberg, Pedro F. Jacob, Thomas Walker, Oliver Barnstedt, Amelia J. Edmondson-Stait, Markus W. Pleijzier, Nils Otto, Philipp Schlegel, Nadiya Sharifi, Emmanuel Perisse, Carlas S. Smith, J. Scott Lauritzen, Marta Costa, Gregory S.X.E. Jefferis, Davi D. Bock, Scott WaddellSummaryAccurately predicting an outcome requires that animals learn supporting and conflicting evidence from sequential experience. In mammals and invertebrates, learned fear responses can be suppressed by experiencing predictive cues without punishment, a process ca...
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Evolutionary Pressure against MHC Class II Binding Cancer Mutations
Publication date: Available online 20 September 2018Source: CellAuthor(s): Rachel Marty, Wesley Kurt Thompson, Rany M. Salem, Maurizio Zanetti, Hannah CarterSummaryThe anti-cancer immune response against mutated peptides of potential immunological relevance (neoantigens) is primarily attributed to MHC-I-restricted cytotoxic CD8+ T cell responses. MHC-II-restricted CD4+ T cells also drive anti-tumor responses, but their relation to neoantigen selection and tumor evolution has not been systematically studied. Modeling the potential of an individual’s MHC-II genotype to present 1,018 driver mutations in 5,942 ...
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

A Neural Circuit for Gut-Induced Reward
Publication date: Available online 20 September 2018Source: CellAuthor(s): Wenfei Han, Luis A. Tellez, Matthew H. Perkins, Isaac O. Perez, Taoran Qu, Jozelia Ferreira, Tatiana L. Ferreira, Daniele Quinn, Zhong-Wu Liu, Xiao-Bing Gao, Melanie M. Kaelberer, Diego V. Bohórquez, Sara J. Shammah-Lagnado, Guillaume de Lartigue, Ivan E. de AraujoSummaryThe gut is now recognized as a major regulator of motivational and emotional states. However, the relevant gut-brain neuronal circuitry remains unknown. We show that optical activation of gut-innervating vagal sensory neurons recapitulates the hallmark effects of stimula...
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Acetate Production from Glucose and Coupling to Mitochondrial Metabolism in Mammals
Publication date: Available online 20 September 2018Source: CellAuthor(s): Xiaojing Liu, Daniel E. Cooper, Ahmad A. Cluntun, Marc O. Warmoes, Steven Zhao, Michael A. Reid, Juan Liu, Peder J. Lund, Mariana Lopes, Benjamin A. Garcia, Kathryn E. Wellen, David G. Kirsch, Jason W. LocasaleSummaryAcetate is a major nutrient that supports acetyl-coenzyme A (Ac-CoA) metabolism and thus lipogenesis and protein acetylation. However, its source is unclear. Here, we report that pyruvate, the end product of glycolysis and key node in central carbon metabolism, quantitatively generates acetate in mammals. This phenomenon becom...
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Human Rad52 Promotes XPG-Mediated R-loop Processing to Initiate Transcription-Associated Homologous Recombination Repair
Publication date: Available online 20 September 2018Source: CellAuthor(s): Takaaki Yasuhara, Reona Kato, Yoshihiko Hagiwara, Bunsyo Shiotani, Motohiro Yamauchi, Shinichiro Nakada, Atsushi Shibata, Kiyoshi MiyagawaSummaryGiven that genomic DNA exerts its function by being transcribed, it is critical for the maintenance of homeostasis that DNA damage, such as double-strand breaks (DSBs), within transcriptionally active regions undergoes accurate repair. However, it remains unclear how this is achieved. Here, we describe a mechanism for transcription-associated homologous recombination repair (TA-HRR) in human cells. The proc...
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Functional Genetic Variants Revealed by Massively Parallel Precise Genome Editing
Publication date: Available online 20 September 2018Source: CellAuthor(s): Eilon Sharon, Shi-An A. Chen, Neil M. Khosla, Justin D. Smith, Jonathan K. Pritchard, Hunter B. FraserSummaryA major challenge in genetics is to identify genetic variants driving natural phenotypic variation. However, current methods of genetic mapping have limited resolution. To address this challenge, we developed a CRISPR-Cas9-based high-throughput genome editing approach that can introduce thousands of specific genetic variants in a single experiment. This enabled us to study the fitness consequences of 16,006 natural genetic variants ...
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

The Energetics and Physiological Impact of Cohesin Extrusion
Publication date: 20 September 2018Source: Cell, Volume 175, Issue 1Author(s): Laura Vian, Aleksandra Pękowska, Suhas S.P. Rao, Kyong-Rim Kieffer-Kwon, Seolkyoung Jung, Laura Baranello, Su-Chen Huang, Laila El Khattabi, Marei Dose, Nathanael Pruett, Adrian L. Sanborn, Andres Canela, Yaakov Maman, Anna Oksanen, Wolfgang Resch, Xingwang Li, Byoungkoo Lee, Alexander L. Kovalchuk, Zhonghui Tang, Steevenson Nelson (Source: Cell)
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

A Thalamic Circuit Lights up Mood
Publication date: 20 September 2018Source: Cell, Volume 175, Issue 1Author(s): Jorge Yanar, Michael M. HalassaThe contributions of areas downstream of retinal ganglion cells involved in the processing and regulation of mood remain largely unspecified. In this issue of Cell, Fernandez et al. (2018) identify a thalamic circuit within the perihabenular region (pHb) linking daily changes of light pattern to mood regulation. (Source: Cell)
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Dynamic Human Environmental Exposome Revealed by Longitudinal Personal Monitoring
Publication date: 20 September 2018Source: Cell, Volume 175, Issue 1Author(s): Chao Jiang, Xin Wang, Xiyan Li, Jingga Inlora, Ting Wang, Qing Liu, Michael SnyderSummaryHuman health is dependent upon environmental exposures, yet the diversity and variation in exposures are poorly understood. We developed a sensitive method to monitor personal airborne biological and chemical exposures and followed the personal exposomes of 15 individuals for up to 890 days and over 66 distinct geographical locations. We found that individuals are potentially exposed to thousands of pan-domain species and chemical compounds, including i...
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Chromatin Domains Go on Repeat in Disease
Publication date: 20 September 2018Source: Cell, Volume 175, Issue 1Author(s): Benoit G. Bruneau, Elphège P. NoraTAD boundaries are insulators of genomic neighborhoods. In this issue, Sun et al. show that disease-associated tandem repeats are located to TAD boundaries and affect their insulation. The findings have important implications for TAD function and mechanisms underlying diseases such as fragile X syndrome and Huntington’s disease. (Source: Cell)
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Human Diseases from Gain-of-Function Mutations in Disordered Protein Regions
Publication date: 20 September 2018Source: Cell, Volume 175, Issue 1Author(s): Xiao-Han Li, M. Madan BabuAlthough there is much focus on the impact of mutations on structured protein domains, less is known about their impact on unstructured regions. In this issue, Meyer et al. demonstrate that mutations resulting in the emergence of new short linear peptide motifs within intrinsically disordered protein regions can cause human genetic diseases by gain of function. (Source: Cell)
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Identification of the Human Skeletal Stem Cell
Publication date: 20 September 2018Source: Cell, Volume 175, Issue 1Author(s): Charles K.F. Chan, Gunsagar S. Gulati, Rahul Sinha, Justin Vincent Tompkins, Michael Lopez, Ava C. Carter, Ryan C. Ransom, Andreas Reinisch, Taylor Wearda, Matthew Murphy, Rachel E. Brewer, Lauren S. Koepke, Owen Marecic, Anoop Manjunath, Eun Young Seo, Tripp Leavitt, Wan-Jin Lu, Allison Nguyen, Stephanie D. Conley, Ankit SalhotraSummaryStem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) th...
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Multi-level Proteomics Identifies CT45 as a Chemosensitivity Mediator and Immunotherapy Target in Ovarian Cancer
This study highlights the power of clinical cancer proteomics to identify targets for chemo- and immunotherapy and illuminate their biological roles.Graphical Abstract (Source: Cell)
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Structural Basis for the RNA-Guided Ribonuclease Activity of CRISPR-Cas13d
Publication date: 20 September 2018Source: Cell, Volume 175, Issue 1Author(s): Cheng Zhang, Silvana Konermann, Nicholas J. Brideau, Peter Lotfy, Xuebing Wu, Scott J. Novick, Timothy Strutzenberg, Patrick R. Griffin, Patrick D. Hsu, Dmitry LyumkisSummaryCRISPR-Cas endonucleases directed against foreign nucleic acids mediate prokaryotic adaptive immunity and have been tailored for broad genetic engineering applications. Type VI-D CRISPR systems contain the smallest known family of single effector Cas enzymes, and their signature Cas13d ribonuclease employs guide RNAs to cleave matching target RNAs. To understand the mol...
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Structural Basis of Smoothened Activation in Hedgehog Signaling
Publication date: 20 September 2018Source: Cell, Volume 175, Issue 1Author(s): Pengxiang Huang, Sanduo Zheng, Bradley M. Wierbowski, Youngchang Kim, Daniel Nedelcu, Laura Aravena, Jing Liu, Andrew C. Kruse, Adrian Salic (Source: Cell)
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Sugar Turns Bacteria Sweet: A Peace Offering in the Gut
Publication date: 20 September 2018Source: Cell, Volume 175, Issue 1Author(s): Ken CadwellFollowing an infection, a subset of individuals can remain disease free despite harboring a pathogen for a prolonged period. In this issue of Cell, Sanchez et al. demonstrate that a metabolically favorable host response can drive an otherwise lethal bacterial pathogen to abandon virulence and become a commensal microorganism. (Source: Cell)
Source: Cell - September 21, 2018 Category: Cytology Source Type: research

Targeting Epigenetic Crosstalk as a Therapeutic Strategy for EZH2-Aberrant Solid Tumors
We report here oncogenic transcriptional reprogramming mediated by MLL1’s interaction with the p300/CBP complex, which directs H3K27me loss to reciprocal H3K27ac gain and restricts EZH2i response. Concurrent inhibition of H3K27me and H3K27ac results in transcriptional repression and MAPK pathway dependency in cancer subsets. In preclinical models encompassing a broad spectrum of EZH2-aberrant solid tumors, a combination of EZH2 and BRD4 inhibitors, or a triple-combination including MAPK inhibition display robust efficacy with very tolerable toxicity. Our results suggest an attractive precision treatment strategy...
Source: Cell - September 14, 2018 Category: Cytology Source Type: research

An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis
Publication date: Available online 13 September 2018Source: CellAuthor(s): Ben Roediger, Quintin Lee, Shweta Tikoo, Joanna C.A. Cobbin, James M. Henderson, Mika Jormakka, Matthew B. O’Rourke, Matthew P. Padula, Natalia Pinello, Marisa Henry, Maria Wynne, Sara F. Santagostino, Cory F. Brayton, Lorna Rasmussen, Leszek Lisowski, Szun S. Tay, David C. Harris, John F. Bertram, John P. Dowling, Patrick BertolinoSummaryThe occurrence of a spontaneous nephropathy with intranuclear inclusions in laboratory mice has puzzled pathologists for over 4 decades, because its etiology remains elusive. The condition is more severe in i...
Source: Cell - September 14, 2018 Category: Cytology Source Type: research

ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activation of S1P
Publication date: Available online 13 September 2018Source: CellAuthor(s): Ju Youn Kim, Ricard Garcia-Carbonell, Shinichiro Yamachika, Peng Zhao, Debanjan Dhar, Rohit Loomba, Randal J. Kaufman, Alan R. Saltiel, Michael KarinSummaryNonalcoholic fatty liver disease (NAFLD) progresses to nonalcoholic steatohepatitis (NASH) in response to elevated endoplasmic reticulum (ER) stress. Whereas the onset of simple steatosis requires elevated de novo lipogenesis, progression to NASH is triggered by accumulation of hepatocyte-free cholesterol. We now show that caspase-2, whose expression is ER-stress inducible and elevated in human a...
Source: Cell - September 14, 2018 Category: Cytology Source Type: research

C. elegans AWA Olfactory Neurons Fire Calcium-Mediated All-or-None Action Potentials
Publication date: Available online 13 September 2018Source: CellAuthor(s): Qiang Liu, Philip B. Kidd, May Dobosiewicz, Cornelia I. BargmannSummaryNeurons in Caenorhabditis elegans and other nematodes have been thought to lack classical action potentials. Unexpectedly, we observe membrane potential spikes with defining characteristics of action potentials in C. elegans AWA olfactory neurons recorded under current-clamp conditions. Ion substitution experiments, mutant analysis, pharmacology, and modeling indicate that AWA fires calcium spikes, which are initiated by EGL-19 voltage-gated CaV1 calcium channels and termina...
Source: Cell - September 14, 2018 Category: Cytology Source Type: research

A Bacterial Chromosome Structuring Protein Binds Overtwisted DNA to Stimulate Type II Topoisomerases and Enable DNA Replication
Publication date: Available online 13 September 2018Source: CellAuthor(s): Monica S. Guo, Diane L. Haakonsen, Wenjie Zeng, Maria A. Schumacher, Michael T. LaubSummaryWhen DNA is unwound during replication, it becomes overtwisted and forms positive supercoils in front of the translocating DNA polymerase. Unless removed or dissipated, this superhelical tension can impede replication elongation. Topoisomerases, including gyrase and topoisomerase IV in bacteria, are required to relax positive supercoils ahead of DNA polymerase but may not be sufficient for replication. Here, we find that GapR, a chromosome structuring protein ...
Source: Cell - September 14, 2018 Category: Cytology Source Type: research

Aster Proteins Facilitate Nonvesicular Plasma Membrane to ER Cholesterol Transport in Mammalian Cells
Publication date: Available online 13 September 2018Source: CellAuthor(s): Jaspreet Sandhu, Shiqian Li, Louise Fairall, Simon G. Pfisterer, Jennifer E. Gurnett, Xu Xiao, Thomas A. Weston, Dipti Vashi, Alessandra Ferrari, Jose L. Orozco, Celine L. Hartman, David Strugatsky, Stephen D. Lee, Cuiwen He, Cynthia Hong, Haibo Jiang, Laurent A. Bentolila, Alberto T. Gatta, Tim P. Levine, Annie FerngSummaryThe mechanisms underlying sterol transport in mammalian cells are poorly understood. In particular, how cholesterol internalized from HDL is made available to the cell for storage or modification is unknown. Here, we describe thr...
Source: Cell - September 14, 2018 Category: Cytology Source Type: research

Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma
Publication date: Available online 13 September 2018Source: CellAuthor(s): Samuel K. McBrayer, Jared R. Mayers, Gabriel J. DiNatale, Diana D. Shi, Januka Khanal, Abhishek A. Chakraborty, Kristopher A. Sarosiek, Kimberly J. Briggs, Alissa K. Robbins, Tomasz Sewastianik, Sarah J. Shareef, Benjamin A. Olenchock, Seth J. Parker, Kensuke Tateishi, Jessica B. Spinelli, Mirazul Islam, Marcia C. Haigis, Ryan E. Looper, Keith L. Ligon, Bradley E. BernsteinSummaryIDH1 mutations are common in low-grade gliomas and secondary glioblastomas and cause overproduction of (R)-2HG. (R)-2HG modulates the activity of many enzymes, including so...
Source: Cell - September 14, 2018 Category: Cytology Source Type: research

A Novel Class of ER Membrane Proteins Regulates ER-Associated Endosome Fission
Publication date: Available online 13 September 2018Source: CellAuthor(s): Melissa J. Hoyer, Patrick J. Chitwood, Christopher C. Ebmeier, Jonathan F. Striepen, Robert Z. Qi, William M. Old, Gia K. VoeltzSummaryEndoplasmic reticulum (ER) membrane contact sites (MCSs) mark positions where endosomes undergo fission for cargo sorting. To define the role of ER at this unique MCS, we targeted a promiscuous biotin ligase to cargo-sorting domains on endosome buds. This strategy identified the ER membrane protein TMCC1, a member of a conserved protein family. TMCC1 concentrates at the ER-endosome MCSs that are spatially and tempora...
Source: Cell - September 14, 2018 Category: Cytology Source Type: research

Balancing Tricks and Mini-pigs: Steps along the Road to Propofol
Publication date: Available online 11 September 2018Source: CellAuthor(s): J.B. Glen (Source: Cell)
Source: Cell - September 11, 2018 Category: Cytology Source Type: research

Chasing Histone Biology from Sea Urchins to Yeast
Publication date: Available online 11 September 2018Source: CellAuthor(s): Together with David Allis, Michael Grunstein just received the Lasker Basic Medical research award. The article that follows is a transcript of a conversation with Jacques Deguine, scientific editor at Cell, that was edited for length. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online. (Source: Cell)
Source: Cell - September 11, 2018 Category: Cytology Source Type: research