Gastroenterology

  • Article
    | Open Access

    Progressive familial intrahepatic cholestasis type 3 is a disease caused by mutations in the gene encoding the multidrug resistance protein 3, and has limited treatment options. Here they show that adeno-associated virus mediated gene therapy prevents disease progression in a mouse disease model.

    • Nicholas D. Weber
    • , Leticia Odriozola
    • , Javier Martínez-García
    • , Veronica Ferrer
    • , Anne Douar
    • , Bernard Bénichou
    • , Gloria González-Aseguinolaza
    •  & Cristian Smerdou
  • Article
    | Open Access

    Gut microbiota alterations, including enrichment of flagellated bacteria, are associated with metabolic syndrome and chronic inflammatory diseases. Here, Tran et al. show, in mice, that elicitation of mucosal anti-flagellin antibodies protects against experimental colitis and ameliorates diet-induced obesity.

    • Hao Q. Tran
    • , Ruth E. Ley
    • , Andrew T. Gewirtz
    •  & Benoit Chassaing
  • Article
    | Open Access

    The adipokine leptin modulates intestinal inflammation in mice. Here the authors describe a patient with inflammatory bowel disease and lipodystrophy, providing evidence that leptin aggravates intestinal inflammation with proinflammatory effects on leukocytes that are reversible by TNFα blockade.

    • Jörn F. Ziegler
    • , Chotima Böttcher
    • , Marilena Letizia
    • , Cansu Yerinde
    • , Hao Wu
    • , Inka Freise
    • , Yasmina Rodriguez-Sillke
    • , Ani K. Stoyanova
    • , Martin E. Kreis
    • , Patrick Asbach
    • , Desiree Kunkel
    • , Josef Priller
    • , Ioannis Anagnostopoulos
    • , Anja A. Kühl
    • , Konstanze Miehle
    • , Michael Stumvoll
    • , Florian Tran
    • , Broder Fredrich
    • , Michael Forster
    • , Andre Franke
    • , Christian Bojarski
    • , Rainer Glauben
    • , Britt-Sabina Löscher
    • , Britta Siegmund
    •  & Carl Weidinger
  • Article
    | Open Access

    Gemcitabine is used to treat gallbaldder cancer but patient responses are variable. Here, the authors use a genome-wide CRISPR screen and identify the translational elongator protein ELP5 as a protein that is important for mediating gemcitabine-induced apoptosis.

    • Sunwang Xu
    • , Ming Zhan
    • , Cen Jiang
    • , Min He
    • , Linhua Yang
    • , Hui Shen
    • , Shuai Huang
    • , Xince Huang
    • , Ruirong Lin
    • , Yongheng Shi
    • , Qiang Liu
    • , Wei Chen
    • , Man Mohan
    •  & Jian Wang
  • Article
    | Open Access

    Higher organisms regulate cellular iron concentrations through Iron Regulatory Proteins (IRPs), which regulate specific messenger RNAs. Here Huynh et al. show that IRP1 requires a Glycogen Branching Enzyme for proper function, and that IRP1 has additional regulatory roles in cell nuclei.

    • Nhan Huynh
    • , Qiuxiang Ou
    • , Pendleton Cox
    • , Roland Lill
    •  & Kirst King-Jones
  • Article
    | Open Access

    Radiofrequency ablation is used to treat metastatic colorectal cancer. In this study, the authors show that incomplete ablation of tumours results in metastases and show in mouse models that the chemokine CCL2 recruits myeloid cells to the partially ablated tumours, which can block T cell function.

    • Liangrong Shi
    • , Junjun Wang
    • , Nianhua Ding
    • , Yi Zhang
    • , Yibei Zhu
    • , Shunli Dong
    • , Xiaohui Wang
    • , Changli Peng
    • , Chunhui Zhou
    • , Ledu Zhou
    • , Xiaodong Li
    • , Hongbing Shi
    • , Wei Wu
    • , Xueyin Long
    • , Changping Wu
    •  & Weihua Liao
  • Article
    | Open Access

    In pancreatic cancer the Kras and Trp53 transgene driven KPC mouse model is used to experimentally study disease processes. Here, the authors analyse tumour evolution within the KPC model, finding both linear and branched evolution and highlighting the utility of this model in mechanistic research of tumour evolution.

    • Noushin Niknafs
    • , Yi Zhong
    • , John Alec Moral
    • , Lance Zhang
    • , Melody Xiaoshan Shao
    • , April Lo
    • , Alvin Makohon-Moore
    • , Christine A. Iacobuzio-Donahue
    •  & Rachel Karchin
  • Article
    | Open Access

    Histone deacetylase 3 (HDAC3) is a regulator of lipid homeostasis in several tissues, however, its role in intestinal lipid metabolism was not yet known. Here the authors study intestine specific HDAC3 knock out mice and report that these animals have increased fatty acid oxidation and undergo remodeling of the intestinal epithelial cell lipidome.

    • Mercedes Dávalos-Salas
    • , Magdalene K. Montgomery
    • , Camilla M. Reehorst
    • , Rebecca Nightingale
    • , Irvin Ng
    • , Holly Anderton
    • , Sheren Al-Obaidi
    • , Analia Lesmana
    • , Cameron M. Scott
    • , Paul Ioannidis
    • , Hina Kalra
    • , Shivakumar Keerthikumar
    • , Lars Tögel
    • , Angela Rigopoulos
    • , Sylvia J. Gong
    • , David S. Williams
    • , Prusoth Yoganantharaja
    • , Kim Bell-Anderson
    • , Suresh Mathivanan
    • , Yann Gibert
    • , Scott Hiebert
    • , Andrew M. Scott
    • , Matthew J. Watt
    •  & John M. Mariadason
  • Article
    | Open Access

    The hepatopancreatic ductal (HPD) system connects both liver and pancreas to the intestine but the molecular details of HPD development are unclear. Here, the authors describe how regionalised Eph/Ephrin signaling regulates HPD morphogenesis by promoting cellular rearrangements leading to an open tube.

    • M. Ilcim Thestrup
    • , Sara Caviglia
    • , Jordi Cayuso
    • , Ronja L. S. Heyne
    • , Racha Ahmad
    • , Wolfgang Hofmeister
    • , Letizia Satriano
    • , David G. Wilkinson
    • , Jesper B. Andersen
    •  & Elke A. Ober
  • Article
    | Open Access

    Predicting the drug response of patients with cancer is crucial for implementing targeted therapy. Here, Su et al. make patient-derived cell lines and perform targeted sequencing and RNA-seq to identify CDKN2A/2B loss as a predictor of response to CDK4/6 inhibitors in esophageal squamous cell carcinoma.

    • Dan Su
    • , Dadong Zhang
    • , Jiaoyue Jin
    • , Lisha Ying
    • , Miao Han
    • , Kaiyan Chen
    • , Bin Li
    • , Junzhou Wu
    • , Zhenghua Xie
    • , Fanrong Zhang
    • , Yihui Lin
    • , Guoping Cheng
    • , Jing-Yu Li
    • , Minran Huang
    • , Jinchao Wang
    • , Kailai Wang
    • , Jianjun Zhang
    • , Fugen Li
    • , Lei Xiong
    • , Andrew Futreal
    •  & Weimin Mao
  • Article
    | Open Access

    The role of the transmembrane glycoprotein CD47 in healing injured intestinal mucosa is unclear. Here, the authors show that selective loss of CD47 in the murine intestinal epithelium results in defective mucosal repair after colonic wounding, with suggested impaired cell migration in vitro.

    • Michelle Reed
    • , Anny-Claude Luissint
    • , Veronica Azcutia
    • , Shuling Fan
    • , Monique N. O’Leary
    • , Miguel Quiros
    • , Jennifer Brazil
    • , Asma Nusrat
    •  & Charles A. Parkos
  • Article
    | Open Access

    Pu-erh tea displays cholesterol-lowering properties. Here, Huang et al. show that this is mostly due to the action of a pigment in Pu-erh tea that induces changes in certain gut microbiota and bile acid levels, thus modulating the gut-liver metabolic axis.

    • Fengjie Huang
    • , Xiaojiao Zheng
    • , Xiaohui Ma
    • , Runqiu Jiang
    • , Wangyi Zhou
    • , Shuiping Zhou
    • , Yunjing Zhang
    • , Sha Lei
    • , Shouli Wang
    • , Junliang Kuang
    • , Xiaolong Han
    • , Meilin Wei
    • , Yijun You
    • , Mengci Li
    • , Yitao Li
    • , Dandan Liang
    • , Jiajian Liu
    • , Tianlu Chen
    • , Chao Yan
    • , Runmin Wei
    • , Cynthia Rajani
    • , Chengxing Shen
    • , Guoxiang Xie
    • , Zhaoxiang Bian
    • , Houkai Li
    • , Aihua Zhao
    •  & Wei Jia
  • Article
    | Open Access

    Impulsive behaviour is common in various neuropsychiatric disorders. Here, the authors identify a pathway from the lateral hypothalamus to the ventral hippocampus and the role of melanin-concentrating hormone signaling in these neurons in specifically regulating impulsivity.

    • Emily E. Noble
    • , Zhuo Wang
    • , Clarissa M. Liu
    • , Elizabeth A. Davis
    • , Andrea N. Suarez
    • , Lauren M. Stein
    • , Linda Tsan
    • , Sarah J. Terrill
    • , Ted M. Hsu
    • , A-Hyun Jung
    • , Lauren M. Raycraft
    • , Joel D. Hahn
    • , Martin Darvas
    • , Alyssa M. Cortella
    • , Lindsey A. Schier
    • , Alexander W. Johnson
    • , Matthew R. Hayes
    • , Daniel P. Holschneider
    •  & Scott E. Kanoski
  • Article
    | Open Access

    Non-invasive early diagnosis of liver fibrosis is important to prevent disease progression and direct treatment strategies. Here the authors developed a collagen-targeting contrast agent for the detection of early stage fibrosis and non-alcoholic steatohepatitis by magnetic resonance and tested it in animal models.

    • Mani Salarian
    • , Ravi Chakra Turaga
    • , Shenghui Xue
    • , Maysam Nezafati
    • , Khan Hekmatyar
    • , Jingjuan Qiao
    • , Yinwei Zhang
    • , Shanshan Tan
    • , Oluwatosin Y. Ibhagui
    • , Yan Hai
    • , Jibiao Li
    • , Rao Mukkavilli
    • , Malvika Sharma
    • , Pardeep Mittal
    • , Xiaoyi Min
    • , Shella Keilholz
    • , Liqing Yu
    • , Gengshen Qin
    • , Alton Brad Farris
    • , Zhi-Ren Liu
    •  & Jenny J. Yang
  • Article
    | Open Access

    Separating different cell compartments from bulk gene expression data can be challenging. Here the authors present DECODER, which can perform de novo deconvolutions on non-negative matrices including microarray, RNA-seq and ATAC-seq data sets.

    • Xianlu Laura Peng
    • , Richard A. Moffitt
    • , Robert J. Torphy
    • , Keith E. Volmar
    •  & Jen Jen Yeh
  • Article
    | Open Access

    In a large prospective cohort of liver transplantation (LT) recipients, the authors identify associations between colonization by multidrug-resistant bacteria (MDRB) and microbiome dysbiosis pre- and post-LT, suggesting colonizing MDRB as an important target for microbiome-informed therapeutic approaches post-LT.

    • Medini K. Annavajhala
    • , Angela Gomez-Simmonds
    • , Nenad Macesic
    • , Sean B. Sullivan
    • , Anna Kress
    • , Sabrina D. Khan
    • , Marla J. Giddins
    • , Stephania Stump
    • , Grace I. Kim
    • , Ryan Narain
    • , Elizabeth C. Verna
    •  & Anne-Catrin Uhlemann
  • Article
    | Open Access

    Activated hepatic stellate cells of putative mesodermal origin orchestrate scarring during injury. Here, the authors define a discrete morphologically plastic lineage of embryonic mesothelial-derived scar-orchestrating cells, through a distinct quiescent adult precursor, defined and paradoxically inhibited by WT1.

    • Timothy James Kendall
    • , Catherine Mary Duff
    • , Luke Boulter
    • , David H. Wilson
    • , Elisabeth Freyer
    • , Stuart Aitken
    • , Stuart John Forbes
    • , John Peter Iredale
    •  & Nicholas Dixon Hastie
  • Article
    | Open Access

    In the treatment of pancreatic ductal adenocarcinoma (PDAC), comorbidities such as cachexia limit quality of life and survival. Here, the authors show TLR7/8 agonist R848 remodels host and tumour immune responses, promoting survival and attenuating cachexia in murine models of PDAC.

    • Katherine A. Michaelis
    • , Mason A. Norgard
    • , Xinxia Zhu
    • , Peter R. Levasseur
    • , Shamilene Sivagnanam
    • , Shannon M. Liudahl
    • , Kevin G. Burfeind
    • , Brennan Olson
    • , Katherine R. Pelz
    • , Diana M. Angeles Ramos
    • , H. Carlo Maurer
    • , Kenneth P. Olive
    • , Lisa M. Coussens
    • , Terry K. Morgan
    •  & Daniel L. Marks
  • Article
    | Open Access

    Resistance to the tyrosine kinase inhibitor Sorafenib, which is the standard treatment for advanced hepatocellular carcinoma, is a major clinical challenge. Here, the authors show that phosphoglycerate dehydrogenase, a key enzyme in the serine synthesis pathway, drives sorafenib resistance.

    • Lai Wei
    • , Derek Lee
    • , Cheuk-Ting Law
    • , Misty Shuo Zhang
    • , Jialing Shen
    • , Don Wai-Ching Chin
    • , Allen Zhang
    • , Felice Ho-Ching Tsang
    • , Ceci Lok-Sze Wong
    • , Irene Oi-Lin Ng
    • , Carmen Chak-Lui Wong
    •  & Chun-Ming Wong
  • Article
    | Open Access

    Dysfunctional autophagy induces inflammation that contributes to tumorigenesis. Here, the authors show that loss of BRG1 impairs autophagy and enhances reactive oxygen species production to disrupt intestinal barrier integrity, leading to spontaneous colitis and subsequent colorectal cancer development.

    • Min Liu
    • , Tongyu Sun
    • , Ni Li
    • , Junjie Peng
    • , Da Fu
    • , Wei Li
    • , Li Li
    •  & Wei-Qiang Gao
  • Article
    | Open Access

    Necrotizing enterocolitis (NEC) is associated with severe neonatal morbidity. Here the authors show, mirroring the NEC phenotype, that IL-23 overexpression in neonates causes malabsorption and decreased expression of intestinal and pancreatic genes mediating food digestion and uptake through IL-22, which directly suppresses pancreatic cell differentiation.

    • Lili Chen
    • , Valentina Strohmeier
    • , Zhengxiang He
    • , Madhura Deshpande
    • , Jovani Catalan-Dibene
    • , Scott K. Durum
    • , Thomas M. Moran
    • , Thomas Kraus
    • , Huabao Xiong
    • , Jeremiah J. Faith
    • , Chhinder P. Sodhi
    • , David J. Hackam
    • , Sergio A. Lira
    •  & Glaucia C. Furtado
  • Article
    | Open Access

    Functional miRNAs derived from the 5p or 3p arm of some miRNA duplexes have opposite roles in cancer progression. Here, the authors show that oncogenic miR-574-5p has greater preference in aggressive gastric cancer as compared with miR-574-3p and this arm preference is partly dependent on complementary targets mediated miRNA decay.

    • Zhengyi Zhang
    • , Jingnan Pi
    • , Dongling Zou
    • , Xiaoshuang Wang
    • , Jiayue Xu
    • , Shan Yu
    • , Ting Zhang
    • , Feng Li
    • , Xianxie Zhang
    • , Hualu Zhao
    • , Fang Wang
    • , Dong Wang
    • , Yanni Ma
    •  & Jia Yu
  • Article
    | Open Access

    Epithelial turnover in the colon requires stem cells in the crypt that express the R-spondin receptor Lgr5. Here, the authors show that regeneration after colon injury involving loss of Lgr5+ and Axin2+ cells requires stromal derived Rspo3-dependent reprogramming of Lgr4+ differentiated cells, including Krt20+ enterocytes.

    • Christine Harnack
    • , Hilmar Berger
    • , Agne Antanaviciute
    • , Ramon Vidal
    • , Sascha Sauer
    • , Alison Simmons
    • , Thomas F. Meyer
    •  & Michael Sigal
  • Article
    | Open Access

    Gastroesophageal reflux disease (GERD) is a major risk factor for Barret’s esophagus (BE) and esophageal adenocarcinoma (EA). Here, An et al. report 25 genetic loci for GERD, many of which associate with BE and EA or with other traits such as BMI.

    • Jiyuan An
    • , Puya Gharahkhani
    • , Matthew H. Law
    • , Jue-Sheng Ong
    • , Xikun Han
    • , Catherine M. Olsen
    • , Rachel E. Neale
    • , John Lai
    • , Tom L. Vaughan
    • , Ines Gockel
    • , René Thieme
    • , Anne C. Böhmer
    • , Janusz Jankowski
    • , Rebecca C. Fitzgerald
    • , Johannes Schumacher
    • , Claire Palles
    • , Marilie D. Gammon
    • , Douglas A. Corley
    • , Nicholas J. Shaheen
    • , Nigel C. Bird
    • , Laura J. Hardie
    • , Liam J. Murray
    • , Brian J. Reid
    • , Wong-Ho Chow
    • , Harvey A. Risch
    • , Weimin Ye
    • , Geoffrey Liu
    • , Yvonne Romero
    • , Leslie Bernstein
    • , Anna H. Wu
    • , M. Agee
    • , B. Alipanahi
    • , A. Auton
    • , R. K. Bell
    • , K. Bryc
    • , S. L. Elson
    • , P. Fontanillas
    • , N. A. Furlotte
    • , D. A. Hinds
    • , K. E. Huber
    • , A. Kleinman
    • , N. K. Litterman
    • , M. H. McIntyre
    • , J. L. Mountain
    • , E. S. Noblin
    • , C. A. M. Northover
    • , S. J. Pitts
    • , J. Fah Sathirapongsasuti
    • , O. V. Sazonova
    • , J. F. Shelton
    • , S. Shringarpure
    • , C. Tian
    • , J. Y. Tung
    • , V. Vacic
    • , C. H. Wilson
    • , David C. Whiteman
    •  & Stuart MacGregor
  • Article
    | Open Access

    Surgical weight-loss interventions improve insulin sensitivity via incompletely understood mechanisms. Here the authors assess skeletal muscle epigenetic changes in individuals with obesity following metabolic surgery and compare them with data from individuals without obesity.

    • Sofiya Gancheva
    • , Meriem Ouni
    • , Tomas Jelenik
    • , Chrysi Koliaki
    • , Julia Szendroedi
    • , Frederico G. S. Toledo
    • , Daniel F. Markgraf
    • , Dominik H. Pesta
    • , Lucia Mastrototaro
    • , Elisabetta De Filippo
    • , Christian Herder
    • , Markus Jähnert
    • , Jürgen Weiss
    • , Klaus Strassburger
    • , Matthias Schlensak
    • , Annette Schürmann
    •  & Michael Roden
  • Article
    | Open Access

    The relationship between metabolomic and behavioral changes is not well understood. Here, the authors analyze metabolome changes in D. melanogaster heads and bodies during hunger and satiety, and develop the Flyscape tool to visualize the resulting metabolic networks and integrate them with other omics data.

    • Daniel Wilinski
    • , Jasmine Winzeler
    • , William Duren
    • , Jenna L. Persons
    • , Kristina J. Holme
    • , Johan Mosquera
    • , Morteza Khabiri
    • , Jason M. Kinchen
    • , Peter L. Freddolino
    • , Alla Karnovsky
    •  & Monica Dus
  • Article
    | Open Access

    While many pleiotropic genetic loci have been identified, how they contribute to phenotypes across traits and diseases is unclear. Here, the authors propose decomposition of genetic associations (DeGAs), which uses singular value decomposition, to characterize the underlying latent structure of genetic associations of 2,138 phenotypes.

    • Yosuke Tanigawa
    • , Jiehan Li
    • , Johanne M. Justesen
    • , Heiko Horn
    • , Matthew Aguirre
    • , Christopher DeBoever
    • , Chris Chang
    • , Balasubramanian Narasimhan
    • , Kasper Lage
    • , Trevor Hastie
    • , Chong Y. Park
    • , Gill Bejerano
    • , Erik Ingelsson
    •  & Manuel A. Rivas
  • Article
    | Open Access

    Retrotransposons are usually dormant in healthy tissue, but become activated during malignancy. Here, in colorectal cancer, Cajuso et al. show that retrotransposon activity associates with clinical features of the disease.

    • Tatiana Cajuso
    • , Päivi Sulo
    • , Tomas Tanskanen
    • , Riku Katainen
    • , Aurora Taira
    • , Ulrika A. Hänninen
    • , Johanna Kondelin
    • , Linda Forsström
    • , Niko Välimäki
    • , Mervi Aavikko
    • , Eevi Kaasinen
    • , Ari Ristimäki
    • , Selja Koskensalo
    • , Anna Lepistö
    • , Laura Renkonen-Sinisalo
    • , Toni Seppälä
    • , Teijo Kuopio
    • , Jan Böhm
    • , Jukka-Pekka Mecklin
    • , Outi Kilpivaara
    • , Esa Pitkänen
    • , Kimmo Palin
    •  & Lauri A. Aaltonen
  • Article
    | Open Access

    IL-36α,β and ɣ are IL-1-related cytokines promoting inflammation in the skin and intestine. Here the authors show they are elevated in individuals with obesity, and that mice lacking the IL-36 receptor antagonist are more resistant to diet-induced obesity and metabolic dysfunction, which depends on intestinal microbiota.

    • Eirini Giannoudaki
    • , Yasmina E. Hernandez-Santana
    • , Kelly Mulfaul
    • , Sarah L. Doyle
    • , Emily Hams
    • , Padraic G. Fallon
    • , Arimin Mat
    • , Donal O’Shea
    • , Manfred Kopf
    • , Andrew E. Hogan
    •  & Patrick T. Walsh
  • Article
    | Open Access

    CD36 is a membrane glycoprotein that has been shown to have tumour promoting or suppressor function depending on tumour type. Here, the authors address CD36 function in colorectal cancer and show it acts as a tumour suppressor by inhibiting B-catenin/myc signalling, resulting in downregulation of glycolysis.

    • Yuan Fang
    • , Zhi-Yong Shen
    • , Yi-Zhi Zhan
    • , Xiao-Chuang Feng
    • , Ke-Li Chen
    • , Yong-Sheng Li
    • , Hai-Jun Deng
    • , Su-Ming Pan
    • , De-Hua Wu
    •  & Yi Ding
  • Article
    | Open Access

    Tumor associated macrophages are functionally and phenotypically heterogeneous. Here the authors describe the spatial distribution of distinct macrophage populations within regions of gastric cancer and probe their associations with clinical outcomes, gene signatures and PDL1 expression.

    • Yu-Kuan Huang
    • , Minyu Wang
    • , Yu Sun
    • , Natasha Di Costanzo
    • , Catherine Mitchell
    • , Adrian Achuthan
    • , John A. Hamilton
    • , Rita A. Busuttil
    •  & Alex Boussioutas
  • Article
    | Open Access

    Activating oncogenic mutations in KRAS and NRAS are common in colorectal cancer, which is a heterogenous disease. Here, the authors show that the RAS mutation spectrum is markedly different between colon and rectal cancer, and also different based on age of diagnosis and microsatellite instability.

    • Ilya G. Serebriiskii
    • , Caitlin Connelly
    • , Garrett Frampton
    • , Justin Newberg
    • , Matthew Cooke
    • , Vince Miller
    • , Siraj Ali
    • , Jeffrey S. Ross
    • , Elizabeth Handorf
    • , Sanjeevani Arora
    • , Christopher Lieu
    • , Erica A. Golemis
    •  & Joshua E. Meyer
  • Article
    | Open Access

    Detection of viral biomarkers is important for disease treatment and prevention. Here, the authors report on a system that uses an electrical pulse-induced electrochemical sensor for the detection of hepatitis E virus, and demonstrate potential application of the device.

    • Ankan Dutta Chowdhury
    • , Kenshin Takemura
    • , Tian-Cheng Li
    • , Tetsuro Suzuki
    •  & Enoch Y. Park
  • Article
    | Open Access

    The effect of diet-induced obesity on intestinal B cell populations is not well understood despite emerging evidence of a critical role for the intestinal immune system in contributing to insulin resistance. Here, the authors show important functions of IgA in regulating metabolic disease and for intestinal immunity in modulating systemic glucose metabolism.

    • Helen Luck
    • , Saad Khan
    • , Justin H. Kim
    • , Julia K. Copeland
    • , Xavier S. Revelo
    • , Sue Tsai
    • , Mainak Chakraborty
    • , Kathleen Cheng
    • , Yi Tao Chan
    • , Mark K. Nøhr
    • , Xavier Clemente-Casares
    • , Marie-Christine Perry
    • , Magar Ghazarian
    • , Helena Lei
    • , Yi-Hsuan Lin
    • , Bryan Coburn
    • , Allan Okrainec
    • , Timothy Jackson
    • , Susan Poutanen
    • , Herbert Gaisano
    • , Johane P. Allard
    • , David S. Guttman
    • , Margaret E. Conner
    • , Shawn Winer
    •  & Daniel A. Winer
  • Article
    | Open Access

    lncRNA and cellular metabolism are frequently dysregulated in cancer. In this study, the authors discover the lncGLCC1 is increased in colorectal cancer cells under glucose starvation conditions and correlates with poor prognosis in this cancer.

    • Jiayin Tang
    • , Tingting Yan
    • , Yujie Bao
    • , Chaoqin Shen
    • , Chenyang Yu
    • , Xiaoqiang Zhu
    • , Xianglong Tian
    • , Fangfang Guo
    • , Qian Liang
    • , Qiang Liu
    • , Ming Zhong
    • , Jinxian Chen
    • , Zhizheng Ge
    • , Xiaobo Li
    • , Xiaoyu Chen
    • , Yun Cui
    • , Yingxuan Chen
    • , Weiping Zou
    • , Haoyan Chen
    • , Jie Hong
    •  & Jing-Yuan Fang
  • Article
    | Open Access

    BTLA is established as a negative regulator of natural killer T (NKT) cell function, and share its ligand HVEM with CD160. Here the authors show, by analyzing NKT activation in CD160-deficient mice or with BTLA blockade, that CD160 synergizes with BTLA to negatively regulate NKT cells during hepatic injury.

    • Tae-Jin Kim
    • , Gayoung Park
    • , Jeongmin Kim
    • , Seon Ah Lim
    • , Jiyoung Kim
    • , Kyungtaek Im
    • , Min Hwa Shin
    • , Yang-Xin Fu
    • , Maria-Luisa Del Rio
    • , Jose-Ignacio Rodriguez-Barbosa
    • , Cassian Yee
    • , Kyung-Suk Suh
    • , Seong-Jin Kim
    • , Sang-Jun Ha
    •  & Kyung-Mi Lee
  • Article
    | Open Access

    The roles played by thrombin in the human intestinal mucosa are unclear. Here, the authors show that the commensal microbiota modulates epithelial production of active thrombin, which controls biofilm growth and contributes to protection of the mucosa from bacterial invasion.

    • Jean-Paul Motta
    • , Alexandre Denadai-Souza
    • , David Sagnat
    • , Laura Guiraud
    • , Anissa Edir
    • , Chrystelle Bonnart
    • , Mireille Sebbag
    • , Perrine Rousset
    • , Ariane Lapeyre
    • , Carine Seguy
    • , Noa Mathurine-Thomas
    • , Heather J. Galipeau
    • , Delphine Bonnet
    • , Laurent Alric
    • , Andre G. Buret
    • , John L. Wallace
    • , Antoine Dufour
    • , Elena F. Verdu
    • , Morley D. Hollenberg
    • , Eric Oswald
    • , Matteo Serino
    • , Celine Deraison
    •  & Nathalie Vergnolle
  • Article
    | Open Access

    The development of brain metastases is a lethal yet poorly understood event in the evolution of many cancers. Here, the authors perform whole-genome and whole-exome sequencing on matched normal, primary and metastatic tissue samples to explore the genomic features of brain metastases in colorectal cancer.

    • Jing Sun
    • , Cheng Wang
    • , Yi Zhang
    • , Lingyan Xu
    • , Weijia Fang
    • , Yuping Zhu
    • , Yi Zheng
    • , Xiaofeng Chen
    • , Xiju Xie
    • , Xinhua Hu
    • , Weidong Hu
    • , Jingyu Zheng
    • , Ping Li
    • , Jian Yu
    • , Zhu Mei
    • , Xiaomin Cai
    • , Biao Wang
    • , Zhibin Hu
    • , Yongqian Shu
    • , Hongbing Shen
    •  & Yanhong Gu
  • Article
    | Open Access

    Alcoholic hepatitis, a common cause of liver failure, lacks effective treatment. Here, the authors show altered hepatic HNF4a isoform expression and hypermethylation of its target genes in patients. HNF4a dysregulation is improved in vitro by TGFb or PPARg modulation suggesting potential therapeutic avenues.

    • Josepmaria Argemi
    • , Maria U. Latasa
    • , Stephen R. Atkinson
    • , Ilya O. Blokhin
    • , Veronica Massey
    • , Joel P. Gue
    • , Joaquin Cabezas
    • , Juan J. Lozano
    • , Derek Van Booven
    • , Aaron Bell
    • , Sheng Cao
    • , Lawrence A. Vernetti
    • , Juan P. Arab
    • , Meritxell Ventura-Cots
    • , Lia R. Edmunds
    • , Constantino Fondevilla
    • , Peter Stärkel
    • , Laurent Dubuquoy
    • , Alexandre Louvet
    • , Gemma Odena
    • , Juan L. Gomez
    • , Tomas Aragon
    • , Jose Altamirano
    • , Juan Caballeria
    • , Michael J. Jurczak
    • , D. Lansing Taylor
    • , Carmen Berasain
    • , Claes Wahlestedt
    • , Satdarshan P. Monga
    • , Marsha Y. Morgan
    • , Pau Sancho-Bru
    • , Philippe Mathurin
    • , Shinji Furuya
    • , Carolin Lackner
    • , Ivan Rusyn
    • , Vijay H. Shah
    • , Mark R. Thursz
    • , Jelena Mann
    • , Matias A. Avila
    •  & Ramon Bataller
  • Article
    | Open Access

    Identifying driver genes in unstable, heterogenous tumour types can be challenging. Here, Mourikis, Benedetti, Foxall and colleagues present a machine learning algorithm to tackle this problem in esophageal adenocarcinoma.

    • Thanos P. Mourikis
    • , Lorena Benedetti
    • , Elizabeth Foxall
    • , Damjan Temelkovski
    • , Joel Nulsen
    • , Juliane Perner
    • , Matteo Cereda
    • , Jesper Lagergren
    • , Michael Howell
    • , Christopher Yau
    • , Rebecca C. Fitzgerald
    • , Paola Scaffidi
    • , Ayesha Noorani
    • , Paul A. W. Edwards
    • , Rachael Fels Elliott
    • , Nicola Grehan
    • , Barbara Nutzinger
    • , Caitriona Hughes
    • , Elwira Fidziukiewicz
    • , Jan Bornschein
    • , Shona MacRae
    • , Jason Crawte
    • , Alex Northrop
    • , Gianmarco Contino
    • , Xiaodun Li
    • , Rachel de la Rue
    • , Annalise Katz-Summercorn
    • , Sujath Abbas
    • , Daniel Loureda
    • , Maria O’Donovan
    • , Ahmad Miremadi
    • , Shalini Malhotra
    • , Monika Tripathi
    • , Simon Tavaré
    • , Andy G. Lynch
    • , Matthew Eldridge
    • , Maria Secrier
    • , Lawrence Bower
    • , Ginny Devonshire
    • , Sriganesh Jammula
    • , Jim Davies
    • , Charles Crichton
    • , Nick Carroll
    • , Peter Safranek
    • , Andrew Hindmarsh
    • , Vijayendran Sujendran
    • , Stephen J. Hayes
    • , Yeng Ang
    • , Andrew Sharrocks
    • , Shaun R. Preston
    • , Sarah Oakes
    • , Izhar Bagwan
    • , Vicki Save
    • , Richard J. E. Skipworth
    • , Ted R. Hupp
    • , J. Robert O’Neill
    • , Olga Tucker
    • , Andrew Beggs
    • , Philippe Taniere
    • , Sonia Puig
    • , Timothy J. Underwood
    • , Robert C. Walker
    • , Ben L. Grace
    • , Hugh Barr
    • , Neil Shepherd
    • , Oliver Old
    • , James Gossage
    • , Andrew Davies
    • , Fuju Chang
    • , Janine Zylstra
    • , Ula Mahadeva
    • , Vicky Goh
    • , Grant Sanders
    • , Richard Berrisford
    • , Catherine Harden
    • , Mike Lewis
    • , Ed Cheong
    • , Bhaskar Kumar
    • , Simon L. Parsons
    • , Irshad Soomro
    • , Philip Kaye
    • , John Saunders
    • , Laurence Lovat
    • , Rehan Haidry
    • , Laszlo Igali
    • , Michael Scott
    • , Sharmila Sothi
    • , Sari Suortamo
    • , Suzy Lishman
    • , George B. Hanna
    • , Christopher J. Peters
    • , Krishna Moorthy
    • , Anna Grabowska
    • , Richard Turkington
    • , Damian McManus
    • , David Khoo
    • , Will Fickling
    •  & Francesca D. Ciccarelli
  • Article
    | Open Access

    Trefoil factor 1 (TFF1) is a protein secreted by the gastric mucosa that protects against gastric tumourigenesis. Here, the authors show that TFF1 inhibits the oncogenic inflammatory response and IL-6-mediated STAT3 activation by interfering with the binding of IL6 to its receptor IL6Rα.

    • Mohammed Soutto
    • , Zheng Chen
    • , Ajaz A. Bhat
    • , Lihong Wang
    • , Shoumin Zhu
    • , Ahmed Gomaa
    • , Andreia Bates
    • , Nadeem S. Bhat
    • , Dunfa Peng
    • , Abbes Belkhiri
    • , M. Blanca Piazuelo
    • , M. Kay Washington
    • , Xi Chen Steven
    • , Richard Peek Jr.
    •  & Wael El-Rifai
  • Article
    | Open Access

    Activated hepatic stellate cells are associated with fibrosis and liver metastases. Here, the authors identify an endogenous role of relaxin in regulating the activation of hepatic stellate cells and report nanoparticle-mediated relaxin gene therapy to mitigate fibrosis and liver metastasis.

    • Mengying Hu
    • , Ying Wang
    • , Ligeng Xu
    • , Sai An
    • , Yu Tang
    • , Xuefei Zhou
    • , Jingjing Li
    • , Rihe Liu
    •  & Leaf Huang
  • Article
    | Open Access

    KRASG12V and BRAFV600E are oncogenic mutations that activate ERK signalling. Here, the authors use single cell analysis in intestinal organoids and show that BRAFV600E activates ERK in all intestinal cell types, while KRASG12V induces ERK activation in only a subset of cells, depending on cell differentiation state.

    • Raphael Brandt
    • , Thomas Sell
    • , Mareen Lüthen
    • , Florian Uhlitz
    • , Bertram Klinger
    • , Pamela Riemer
    • , Claudia Giesecke-Thiel
    • , Silvia Schulze
    • , Ismail Amr El-Shimy
    • , Desiree Kunkel
    • , Beatrix Fauler
    • , Thorsten Mielke
    • , Norbert Mages
    • , Bernhard G. Herrmann
    • , Christine Sers
    • , Nils Blüthgen
    •  & Markus Morkel
  • Article
    | Open Access

    Clinical and molecular heterogeneity of ulcerative colitis presents unresolved challenges to identify predictive biomarkers of response to therapies. Here, the authors combine mouse colitis time course with patient biopsy transcriptomes, achieving unsupervised clustering of UC patients correlating with therapeutic outcomes in independent data sets.

    • Paulo Czarnewski
    • , Sara M. Parigi
    • , Chiara Sorini
    • , Oscar E. Diaz
    • , Srustidhar Das
    • , Nicola Gagliani
    •  & Eduardo J. Villablanca
  • Article
    | Open Access

    Mast cells within the tumor microenvironment have controversial roles. Here, the authors show, using genetic mouse models, that in gastric cancer, mast cells at the periphery of the tumors are activated via cancer cell produced-IL33 and promote tumorigenesis by recruiting macrophages within the tumors.

    • Moritz F. Eissmann
    • , Christine Dijkstra
    • , Andrew Jarnicki
    • , Toby Phesse
    • , Jamina Brunnberg
    • , Ashleigh R. Poh
    • , Nima Etemadi
    • , Evelyn Tsantikos
    • , Stefan Thiem
    • , Nicholas D. Huntington
    • , Margaret L. Hibbs
    • , Alex Boussioutas
    • , Michele A. Grimbaldeston
    • , Michael Buchert
    • , Robert J. J. O’Donoghue
    • , Frederick Masson
    •  & Matthias Ernst
  • Article
    | Open Access

    Distinguishing clinical subtypes of IBD is critical for optimal treatments, outcome prediction, and better understanding of disease pathogenesis. Here the authors phenotype blood and intestinal immune cells by mass cytometry and identify signatures associated with distinct disease states.

    • Samuel J. S. Rubin
    • , Lawrence Bai
    • , Yeneneh Haileselassie
    • , Gotzone Garay
    • , Chohee Yun
    • , Laren Becker
    • , Sarah E. Streett
    • , Sidhartha R. Sinha
    •  & Aida Habtezion
  • Article
    | Open Access

    EZH2-mediated methylatation of histone 3 is essential for immune regulation. Here, the authors show that EZH2 inhibitors attenuate experimental colitis in mice by promoting the development of myeloid-derived suppressor cells, and delay the onset of colitis-associated cancer.

    • Jie Zhou
    • , Shuo Huang
    • , Zhongyu Wang
    • , Jiani Huang
    • , Liang Xu
    • , Xuefeng Tang
    • , Yisong Y. Wan
    • , Qi-jing Li
    • , Alistair L. J. Symonds
    • , Haixia Long
    •  & Bo Zhu
  • Article
    | Open Access

    The gut microbiome has been reported to be associated with obesity; here, the authors show that there are sex-specific differences in the relationship between gut microbes and abdominal obesity.

    • Yan Min
    • , Xiaoguang Ma
    • , Kris Sankaran
    • , Yuan Ru
    • , Lijin Chen
    • , Mike Baiocchi
    •  & Shankuan Zhu