Gastroenterology

  • Article | | open

    Whether the Wnt enhanceosome’ components BCL9/9l can affect intestinal homeostasis and tumorigenesis is still unclear. Using conditional Bcl9/9l KO mice, the authors of this study show that the BCL9/9l complex is required for intestinal stem cells to drive tissue regeneration and that loss of BCL9/9l suppresses Wnt-driven transformation.

    • David M. Gay
    • , Rachel A. Ridgway
    • , Miryam Müeller
    • , Michael C. Hodder
    • , Ann Hedley
    • , William Clark
    • , Joshua D. Leach
    • , Rene Jackstadt
    • , Colin Nixon
    • , David J. Huels
    • , Andrew D. Campbell
    • , Thomas G. Bird
    •  & Owen J. Sansom
  • Article | | open

    Reduction in food intake elicits neuroendocrine adaptations to counterregulate the negative energy balance, e.g. via reduction in leptin levels. Here, the authors identify an additional starvation signal, growth hormone (GH). Blocking GH receptor attenuates the fall of whole body energy expenditure during food deprivation in mice.

    • Isadora C. Furigo
    • , Pryscila D. S. Teixeira
    • , Gabriel O. de Souza
    • , Gisele C. L. Couto
    • , Guadalupe García Romero
    • , Mario Perelló
    • , Renata Frazão
    • , Lucila L. Elias
    • , Martin Metzger
    • , Edward O. List
    • , John J. Kopchick
    •  & Donato J. Jr
  • Article | | open

    MicroRNA miR-500a-5p has been linked to oncogenesis but its role in colorectal cancer (CRC) is largely unknown. Here, the authors investigate the role of miR-500a-5p in CRC in vitro and in vivo models and find that miR-500a-5p acts as a tumour suppressor in CRC by targeting the p300/YY1/HDAC2 axis.

    • Weimei Tang
    • , Weijie Zhou
    • , Li Xiang
    • , Xiaosheng Wu
    • , Pei Zhang
    • , Jing Wang
    • , Guangnan Liu
    • , Wenjing Zhang
    • , Ying Peng
    • , Xiaoting Huang
    • , Jianqun Cai
    • , Yang Bai
    • , Lan Bai
    • , Wei Zhu
    • , Hongxiang Gu
    • , Jing Xiong
    • , Chen Ye
    • , Aimin Li
    • , Side Liu
    •  & Jide Wang
  • Article | | open

    Individuals show large variability in their capacity to lose weight and maintain this weight. Here, the authors perform GWAS in two weight loss intervention cohorts and identify two genetic loci associated with weight loss that are taken forward for Bayesian fine-mapping and functional assessment in flies.

    • Armand Valsesia
    • , Qiao-Ping Wang
    • , Nele Gheldof
    • , Jérôme Carayol
    • , Hélène Ruffieux
    • , Teleri Clark
    • , Victoria Shenton
    • , Lisa J. Oyston
    • , Gregory Lefebvre
    • , Sylviane Metairon
    • , Christian Chabert
    • , Ondine Walter
    • , Polina Mironova
    • , Paulina Lau
    • , Patrick Descombes
    • , Nathalie Viguerie
    • , Dominique Langin
    • , Mary-Ellen Harper
    • , Arne Astrup
    • , Wim H. Saris
    • , Robert Dent
    • , Greg G. Neely
    •  & Jörg Hager
  • Article | | open

    Obesity is associated with altered N-acylethanolamine levels (NAE). Here the authors show that deletion of the gene encoding N-acylphosphatidylethanolamine phospholipase D, a key enzyme for NAE synthesis, in intestinal cells of mice leads to the development of obesity and hepatic steatosis via a mechanism involving the gut-brain axis.

    • Amandine Everard
    • , Hubert Plovier
    • , Marialetizia Rastelli
    • , Matthias Van Hul
    • , Alice de Wouters d’Oplinter
    • , Lucie Geurts
    • , Céline Druart
    • , Sylvie Robine
    • , Nathalie M. Delzenne
    • , Giulio G. Muccioli
    • , Willem M. de Vos
    • , Serge Luquet
    • , Nicolas Flamand
    • , Vincenzo Di Marzo
    •  & Patrice D. Cani
  • Article | | open

    Somatic alterations in the exonuclease domain of DNA polymerase ɛ have been linked to the development of highly mutated cancers. Here, the authors report that a major consequence of the most common cancer-associated Polɛ variant is a dramatically increased DNA polymerase activity.

    • Xuanxuan Xing
    • , Daniel P. Kane
    • , Chelsea R. Bulock
    • , Elizabeth A. Moore
    • , Sushma Sharma
    • , Andrei Chabes
    •  & Polina V. Shcherbakova
  • Article | | open

    Obesity and the distribution of fat within the body are risk factors for cardiometabolic diseases. Here, Rask-Andersen et al. perform GWAS for bio-electrical impedance measurements in UK Biobank participants and identify 29 novel independent loci for fat distribution and a high degree of sex-heterogeneity.

    • Mathias Rask-Andersen
    • , Torgny Karlsson
    • , Weronica E. Ek
    •  & Åsa Johansson
  • Article | | open

    There are distinct hypermethylation patterns in gene promoters in hepatocellular carcinomas (HCCs). Here, the authors show that the enhancer of C/EBPβ is recurrently hypomethylated in human HCCs, recapitulating this in a transgenic murine model and linking aberrant enhancer hypomethylation to hepatocarcinogenesis.

    • Lei Xiong
    • , Feng Wu
    • , Qiong Wu
    • , Liangliang Xu
    • , Otto K. Cheung
    • , Wei Kang
    • , Myth T. Mok
    • , Lemuel L. M. Szeto
    • , Cheuk-Yin Lun
    • , Raymond W. Lung
    • , Jinglin Zhang
    • , Ken H. Yu
    • , Sau-Dan Lee
    • , Guangcun Huang
    • , Chiou-Miin Wang
    • , Joseph Liu
    • , Zhuo Yu
    • , Dae-Yeul Yu
    • , Jian-Liang Chou
    • , Wan-Hong Huang
    • , Bo Feng
    • , Yue-Sun Cheung
    • , Paul B. Lai
    • , Patrick Tan
    • , Nathalie Wong
    • , Michael W. Chan
    • , Tim H. Huang
    • , Kevin Y. Yip
    • , Alfred S. Cheng
    •  & Ka-Fai To
  • Article | | open

    Agouti-related peptide (AgRP) producing neurons regulate food intake and metabolic processes in peripheral organs. Here, the authors show that hypothalamic AgRP neurons alter whole body substrate utilization to favour carbohydrate usage and lipid storage.

    • João Paulo Cavalcanti-de-Albuquerque
    • , Jeremy Bober
    • , Marcelo R. Zimmer
    •  & Marcelo O. Dietrich
  • Article | | open

    The humoral immune response role in cancer is unclear. Here the authors perform an in-depth proteomic profiling of immunoglobulin-bound proteins in plasma from pancreatic ductal adenocarcinoma patients and find cancer-cell specific antibodies neutralized by binding to cancer-cell derived exosomes.

    • Michela Capello
    • , Jody V. Vykoukal
    • , Hiroyuki Katayama
    • , Leonidas E. Bantis
    • , Hong Wang
    • , Deepali L. Kundnani
    • , Clemente Aguilar-Bonavides
    • , Mitzi Aguilar
    • , Satyendra C. Tripathi
    • , Dilsher S. Dhillon
    • , Amin A. Momin
    • , Haley Peters
    • , Matthew H. Katz
    • , Hector Alvarez
    • , Vincent Bernard
    • , Sammy Ferri-Borgogno
    • , Randall Brand
    • , Douglas G. Adler
    • , Matthew A. Firpo
    • , Sean J. Mulvihill
    • , Jeffrey J. Molldrem
    • , Ziding Feng
    • , Ayumu Taguchi
    • , Anirban Maitra
    •  & Samir M. Hanash
  • Article | | open

    The generation of protective secretory IgA is a desired outcome of oral vaccination. Here, the authors show that the depletion of intestinal ATP significantly improves the production and response of high-affinity IgA against both live and inactivated oral vaccines.

    • Michele Proietti
    • , Lisa Perruzza
    • , Daniela Scribano
    • , Giovanni Pellegrini
    • , Rocco D’Antuono
    • , Francesco Strati
    • , Marco Raffaelli
    • , Santiago F. Gonzalez
    • , Marcus Thelen
    • , Wolf-Dietrich Hardt
    • , Emma Slack
    • , Mauro Nicoletti
    •  & Fabio Grassi
  • Article | | open

    Chronic hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC) and is associated with immune tolerance to HBV. Here the authors show, in a transgenic mouse model, that rescuing T cells function via inhibition of co-inhibitory receptor TIGIT results in HCC development via supporting inflammation.

    • Lu Zong
    • , Hui Peng
    • , Cheng Sun
    • , Fenglei Li
    • , Meijuan Zheng
    • , Yongyan Chen
    • , Haiming Wei
    • , Rui Sun
    •  & Zhigang Tian
  • Article | | open

    Deregulation of the RAS GTPase cycle due to mutations in RAS genes is commonly associated with cancer development. Here authors use NMR and mass spectrometry to shows that KRAS phosphorylation via Src alters the conformation of switch I and II regions and thereby impacts the GTPase cycle.

    • Yoshihito Kano
    • , Teklab Gebregiworgis
    • , Christopher B. Marshall
    • , Nikolina Radulovich
    • , Betty P. K. Poon
    • , Jonathan St-Germain
    • , Jonathan D. Cook
    • , Ivette Valencia-Sama
    • , Benjamin M. M. Grant
    • , Silvia Gabriela Herrera
    • , Jinmin Miao
    • , Brian Raught
    • , Meredith S. Irwin
    • , Jeffrey E. Lee
    • , Jen Jen Yeh
    • , Zhong-Yin Zhang
    • , Ming-Sound Tsao
    • , Mitsuhiko Ikura
    •  & Michael Ohh
  • Article | | open

    Animal studies have shown that the nutritional status of parents can predispose the offspring to obesity and obesity-related diseases. Here the authors show that cardiac dysfunction induced by a high-fat diet persists for two generations in Drosophila, and that targeted expression of ATGL/bmm in the offspring, as well as inhibition of H3K27 trimethylation, is cardioprotective.

    • Maria Clara Guida
    • , Ryan Tyge Birse
    • , Alessandra Dall’Agnese
    • , Paula Coutinho Toto
    • , Soda Balla Diop
    • , Antonello Mai
    • , Peter D. Adams
    • , Pier Lorenzo Puri
    •  & Rolf Bodmer
  • Article | | open

    Wilms tumor gene on the X chromosome (WTX) is commonly downregulated in human cancers. Here the authors show that in colorectal cancer (CRC) WTX expression is downregulated via miR20a and miR160a and its loss promotes tumor development and liver metastasis by disrupting the interaction between RhoGDIα and CDC42 leading to the activation of the CDC42 downstream cascades.

    • Gui-fang Zhu
    • , Yang-wei Xu
    • , Jian Li
    • , Hui-lin Niu
    • , Wen-xia Ma
    • , Jia Xu
    • , Pei-rong Zhou
    • , Xia Liu
    • , Dan-li Ye
    • , Xiao-rong Liu
    • , Tao Yan
    • , Wei-ke Zhai
    • , Zhi-jun Xu
    • , Chun Liu
    • , Lei Wang
    • , Hao Wang
    • , Jia-mao Luo
    • , Li Liu
    • , Xuan-qi Li
    • , Suiqun Guo
    • , Hui-ping Jiang
    • , Peng Shen
    • , Hui-kuan Lin
    • , Di-hua Yu
    • , Yan-qing Ding
    •  & Qing-ling Zhang
  • Article | | open

    Urolithins are microbial metabolites derived from food polyphenols. Here, Singh et al. show that urolithin A and a synthetic analogue enhance gut barrier function via Nrf2-dependent pathways and mitigate inflammation and colitis in mice, highlighting a potential application for inflammatory bowel diseases.

    • Rajbir Singh
    • , Sandeep Chandrashekharappa
    • , Sobha R. Bodduluri
    • , Becca V. Baby
    • , Bindu Hegde
    • , Niranjan G. Kotla
    • , Ankita A. Hiwale
    • , Taslimarif Saiyed
    • , Paresh Patel
    • , Matam Vijay-Kumar
    • , Morgan G. I. Langille
    • , Gavin M. Douglas
    • , Xi Cheng
    • , Eric C. Rouchka
    • , Sabine J. Waigel
    • , Gerald W. Dryden
    • , Houda Alatassi
    • , Huang-Ge Zhang
    • , Bodduluri Haribabu
    • , Praveen K. Vemula
    •  & Venkatakrishna R. Jala
  • Article | | open

    TOP1MT is a topoisomerase that is localised to mitochondria. Here, the authors show that TOP1MT has a tumor promoting role in hepatocellular carcinoma by supporting mitochondrial translation and that its deficiency limits tumorigenicity.

    • S. A. Baechler
    • , V. M. Factor
    • , I. Dalla Rosa
    • , A. Ravji
    • , D. Becker
    • , S. Khiati
    • , L. M. Miller Jenkins
    • , M. Lang
    • , C. Sourbier
    • , S. A. Michaels
    • , L. M. Neckers
    • , H. L. Zhang
    • , A. Spinazzola
    • , S. N. Huang
    • , J. U. Marquardt
    •  & Y. Pommier
  • Article | | open

    The human stomach is divided into seven anatomically distinct regions but their protein composition is largely unknown. Here, the authors present a region-resolved map of the healthy human stomach mucosa as well as mucosa proteomes of tumor and tumor nearby tissue from gastric cancer patients.

    • Xiaotian Ni
    • , Zhaoli Tan
    • , Chen Ding
    • , Chunchao Zhang
    • , Lan Song
    • , Shuai Yang
    • , Mingwei Liu
    • , Ru Jia
    • , Chuanhua Zhao
    • , Lei Song
    • , Wanlin Liu
    • , Quan Zhou
    • , Tongqing Gong
    • , Xianju Li
    • , Yanhong Tai
    • , Weimin Zhu
    • , Tieliu Shi
    • , Yi Wang
    • , Jianming Xu
    • , Bei Zhen
    •  & Jun Qin
  • Article | | open

    The severity of ulcerative colitis, and response to treatment, is highly variable. Here, the authors examine rectal gene expression signatures and faecal microbiomes of children and adults with the disease and provide new insights in to pathogenesis.

    • Yael Haberman
    • , Rebekah Karns
    • , Phillip J. Dexheimer
    • , Melanie Schirmer
    • , Judith Somekh
    • , Ingrid Jurickova
    • , Tzipi Braun
    • , Elizabeth Novak
    • , Laura Bauman
    • , Margaret H. Collins
    • , Angela Mo
    • , Michael J. Rosen
    • , Erin Bonkowski
    • , Nathan Gotman
    • , Alison Marquis
    • , Mason Nistel
    • , Paul A. Rufo
    • , Susan S. Baker
    • , Cary G. Sauer
    • , James Markowitz
    • , Marian D. Pfefferkorn
    • , Joel R. Rosh
    • , Brendan M. Boyle
    • , David R. Mack
    • , Robert N. Baldassano
    • , Sapana Shah
    • , Neal S. Leleiko
    • , Melvin B. Heyman
    • , Anne M. Grifiths
    • , Ashish S. Patel
    • , Joshua D. Noe
    • , Bruce J. Aronow
    • , Subra Kugathasan
    • , Thomas D. Walters
    • , Greg Gibson
    • , Sonia Davis Thomas
    • , Kevin Mollen
    • , Shai Shen-Orr
    • , Curtis Huttenhower
    • , Ramnik J. Xavier
    • , Jeffrey S. Hyams
    •  & Lee A. Denson
  • Article | | open

    Tr1 cells are considered an immunosuppressive CD4 T cell population producing IL-10. Here the authors show that IL-10 is insufficient for Tr1 immunosuppression, define surface markers and transcriptional program of the immunosuppressive subset within Tr1, and reveal its deficiency in patients with IBD.

    • Leonie Brockmann
    • , Shiwa Soukou
    • , Babett Steglich
    • , Paulo Czarnewski
    • , Lilan Zhao
    • , Sandra Wende
    • , Tanja Bedke
    • , Can Ergen
    • , Carolin Manthey
    • , Theodora Agalioti
    • , Maria Geffken
    • , Oliver Seiz
    • , Sara M. Parigi
    • , Chiara Sorini
    • , Jens Geginat
    • , Keishi Fujio
    • , Thomas Jacobs
    • , Thomas Roesch
    • , Jacob R. Izbicki
    • , Ansgar W. Lohse
    • , Richard A. Flavell
    • , Christian Krebs
    • , Jan-Ake Gustafsson
    • , Per Antonson
    • , Maria Grazia Roncarolo
    • , Eduardo J. Villablanca
    • , Nicola Gagliani
    •  & Samuel Huber
  • Article | | open

    Developing new technologies for the neuromodulation of the vagus nerve can enable therapeutic strategies for body weight control in obese patients. Here, the authors present a battery-free self-powered implantable vagus nerve stimulation system that electrically responds to stomach movement.

    • Guang Yao
    • , Lei Kang
    • , Jun Li
    • , Yin Long
    • , Hao Wei
    • , Carolina A. Ferreira
    • , Justin J. Jeffery
    • , Yuan Lin
    • , Weibo Cai
    •  & Xudong Wang
  • Article | | open

    Cyclins A2 and E1 are known to regulate the cell cycle by promoting S phase entry and progression. Here, they identify an aggressive hepatocellular carcinoma subgroup exhibiting cyclin activation through various mechanisms and find this subgroup to display replication stress-induced structural rearrangements frequently activating TERT promoter.

    • Quentin Bayard
    • , Léa Meunier
    • , Camille Peneau
    • , Victor Renault
    • , Jayendra Shinde
    • , Jean-Charles Nault
    • , Iadh Mami
    • , Gabrielle Couchy
    • , Giuliana Amaddeo
    • , Emmanuel Tubacher
    • , Delphine Bacq
    • , Vincent Meyer
    • , Tiziana La Bella
    • , Audrey Debaillon-Vesque
    • , Paulette Bioulac-Sage
    • , Olivier Seror
    • , Jean-Frédéric Blanc
    • , Julien Calderaro
    • , Jean-François Deleuze
    • , Sandrine Imbeaud
    • , Jessica Zucman-Rossi
    •  & Eric Letouzé
  • Article | | open

    Cubilin and the transmembrane protein amnionless (AMN) form the endocytic receptor cubam that is essential for intestinal vitamin B12 uptake. Here the authors present the 2.3 Å crystal structure of AMN in complex with the amino-terminal region of cubilin and discuss cubam architecture and disease causing mutations.

    • Casper Larsen
    • , Anders Etzerodt
    • , Mette Madsen
    • , Karsten Skjødt
    • , Søren Kragh Moestrup
    •  & Christian Brix Folsted Andersen
  • Article | | open

    Obesity increases the risk of hepatocellular carcinoma (HCC) especially in men. Here the authors find a potential mechanistic explanation by showing that, in mice, obesity-induced STAT3 cooperates with the androgen receptor to activate the mTORC pathway through up regulation of CCRK, resulting in hepatic steatosis worsening and HCC development via metabolic and immune reprogramming.

    • Hanyong Sun
    • , Weiqin Yang
    • , Yuan Tian
    • , Xuezhen Zeng
    • , Jingying Zhou
    • , Myth T. S. Mok
    • , Wenshu Tang
    • , Yu Feng
    • , Liangliang Xu
    • , Anthony W. H. Chan
    • , Joanna H. Tong
    • , Yue-Sun Cheung
    • , Paul B. S. Lai
    • , Hector K. S. Wang
    • , Shun-Wa Tsang
    • , King-Lau Chow
    • , Mengying Hu
    • , Rihe Liu
    • , Leaf Huang
    • , Bing Yang
    • , Pengyuan Yang
    • , Ka-Fai To
    • , Joseph J. Y. Sung
    • , Grace L. H. Wong
    • , Vincent W. S. Wong
    •  & Alfred S. L. Cheng
  • Article | | open

    Faecal microbiota transplantation (FMT) is becoming a therapeutic option in several gastrointestinal disorders. Here, Burrello et al. study the immunological mechanisms by which FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis in a mouse model of colitis.

    • Claudia Burrello
    • , Federica Garavaglia
    • , Fulvia Milena Cribiù
    • , Giulia Ercoli
    • , Gianluca Lopez
    • , Jacopo Troisi
    • , Angelo Colucci
    • , Silvia Guglietta
    • , Sara Carloni
    • , Simone Guglielmetti
    • , Valentina Taverniti
    • , Giulia Nizzoli
    • , Silvano Bosari
    • , Flavio Caprioli
    • , Maria Rescigno
    •  & Federica Facciotti
  • Article | | open

    Anemia has a global prevalence of over 2 billion people and is diagnosed via blood-based laboratory test. Here the authors describe a smartphone app that can estimate hemoglobin levels and detect anemia by analyzing pictures of fingernail beds taken with a smartphone and without the need of any external equipment.

    • Robert G. Mannino
    • , David R. Myers
    • , Erika A. Tyburski
    • , Christina Caruso
    • , Jeanne Boudreaux
    • , Traci Leong
    • , G. D. Clifford
    •  & Wilbur A. Lam
  • Article | | open

    A role for Slit/Robo signalling in pancreas development has not been defined. Here, the authors generate Robo1/Robo2 knockout mice to identify both as needed for establishing initial pancreatic cell identity as well as for proliferation and survival of pancreatic progenitors.

    • Sophie Escot
    • , David Willnow
    • , Heike Naumann
    • , Silvia Di Francescantonio
    •  & Francesca M. Spagnoli
  • Article | | open

    Genome-wide association studies have so far identified eight risk loci for gallstone disease. Here, the authors perform meta-analysis in cohorts from Iceland and the UK which reveals further 21 common and low-frequency risk variants that highlight the role of bile acid homeostasis in gallstone disease.

    • Egil Ferkingstad
    • , Asmundur Oddsson
    • , Solveig Gretarsdottir
    • , Stefania Benonisdottir
    • , Gudmar Thorleifsson
    • , Aimee M. Deaton
    • , Stefan Jonsson
    • , Olafur A. Stefansson
    • , Gudmundur L. Norddahl
    • , Florian Zink
    • , Gudny A. Arnadottir
    • , Bjarni Gunnarsson
    • , Gisli H. Halldorsson
    • , Anna Helgadottir
    • , Brynjar O. Jensson
    • , Ragnar P. Kristjansson
    • , Gardar Sveinbjornsson
    • , David A. Sverrisson
    • , Gisli Masson
    • , Isleifur Olafsson
    • , Gudmundur I. Eyjolfsson
    • , Olof Sigurdardottir
    • , Hilma Holm
    • , Ingileif Jonsdottir
    • , Sigurdur Olafsson
    • , Thora Steingrimsdottir
    • , Thorunn Rafnar
    • , Einar S. Bjornsson
    • , Unnur Thorsteinsdottir
    • , Daniel F. Gudbjartsson
    • , Patrick Sulem
    •  & Kari Stefansson
  • Article | | open

    SLIT-ROBO alterations arise in pancreatic ductal adenocarcinoma (PDAC), but their role in the pancreas is unclear. Here, the authors use mouse models to show that loss of epithelial Robo2 activates the neighbouring stroma via TGF-β signalling; findings  are relevant to PDAC patients, where ROBO expression correlates with survival outcomes.

    • Andreia V. Pinho
    • , Mathias Van Bulck
    • , Lorraine Chantrill
    • , Mehreen Arshi
    • , Tatyana Sklyarova
    • , David Herrmann
    • , Claire Vennin
    • , David Gallego-Ortega
    • , Amanda Mawson
    • , Marc Giry-Laterriere
    • , Astrid Magenau
    • , Gunther Leuckx
    • , Luc Baeyens
    • , Anthony J. Gill
    • , Phoebe Phillips
    • , Paul Timpson
    • , Andrew V. Biankin
    • , Jianmin Wu
    •  & Ilse Rooman
  • Article | | open

    Inflammatory diseases of the pancreas are currently untreatable and lack a pre-clinical model that recapitulates the hallmarks of the human pathology. Here, the authors generate a knock-in mouse strain with increased tripsinogen autoactivation and show that it develops spontaneous pancreatic pathology with some key features of human pancreatitis.

    • Andrea Geisz
    •  & Miklós Sahin-Tóth
  • Article | | open

    Neonatal rotavirus infections are associated with gastrointestinal symptoms in some settings, but the role of host factors in clinical presentation is unclear. Here, Ramani et al. show that human milk oligosaccharides and microbiome are associated with symptomatic infection with neonatal strain G10P[11].

    • Sasirekha Ramani
    • , Christopher J. Stewart
    • , Daniel R. Laucirica
    • , Nadim J. Ajami
    • , Bianca Robertson
    • , Chloe A. Autran
    • , Dhairyasheel Shinge
    • , Sandya Rani
    • , Sasirekha Anandan
    • , Liya Hu
    • , Josephine C. Ferreon
    • , Kurien A. Kuruvilla
    • , Joseph F. Petrosino
    • , B. V. Venkataram Prasad
    • , Lars Bode
    • , Gagandeep Kang
    •  & Mary K. Estes
  • Article | | open

    Pancreatic ductal adenocarcinoma (PDAC) cells display varying degrees of reliance on oncogenic KRAS. Here the authors show that KRAS-resistant PDAC cells maintain nucleotides synthesis through a KRAS-independent upregulation of the non-oxidative pentose phosphate pathway gene RPIA and that targeting nucleotide metabolism restore sensitivity to KRAS pathway inhibition.

    • Naiara Santana-Codina
    • , Anjali A. Roeth
    • , Yi Zhang
    • , Annan Yang
    • , Oksana Mashadova
    • , John M. Asara
    • , Xiaoxu Wang
    • , Roderick T. Bronson
    • , Costas A. Lyssiotis
    • , Haoqiang Ying
    •  & Alec C. Kimmelman
  • Article | | open

    The mammalian stomach is a complex organ with diverse roles in health and disease. Here, the authors integrate proteomics and transcriptomics to analyze the mouse stomach at 15 time points during development, providing molecular level insights into system-wide developmental changes.

    • Xianju Li
    • , Chunchao Zhang
    • , Tongqing Gong
    • , Xiaotian Ni
    • , Jin’e Li
    • , Dongdong Zhan
    • , Mingwei Liu
    • , Lei Song
    • , Chen Ding
    • , Jianming Xu
    • , Bei Zhen
    • , Yi Wang
    •  & Jun Qin
  • Article | | open

    Hippo-YAP pathway plays an important role in cancers; however the in vivo relevance of YAP/TAZ target genes is unclear. Here, the authors show that NUAK2 is a target of YAP and participates in a feedback loop to maximize YAP activity. Inhibition of NUAK2 suppresses YAP-driven hepatomegaly and liver cancer growth, offering a new target for cancer therapy.

    • Wei-Chien Yuan
    • , Brian Pepe-Mooney
    • , Giorgio G. Galli
    • , Michael T. Dill
    • , Hai-Tsang Huang
    • , Mingfeng Hao
    • , Yumeng Wang
    • , Han Liang
    • , Raffaele A. Calogero
    •  & Fernando D. Camargo
  • Article | | open

    No effective pharmacological treatments exist for nonalcoholic fatty liver disease (NAFLD). Here, the authors show that serotonin concentration in the portal blood is increased in nine human subjects and in mice fed a high-fat diet, and that local serotonin signaling ablation, either genetically or with an antagonist, prevents hepatic steatosis in mice.

    • Wonsuk Choi
    • , Jun Namkung
    • , Inseon Hwang
    • , Hyeongseok Kim
    • , Ajin Lim
    • , Hye Jung Park
    • , Hye Won Lee
    • , Kwang-Hyub Han
    • , Seongyeol Park
    • , Ji-Seon Jeong
    • , Geul Bang
    • , Young Hwan Kim
    • , Vijay K. Yadav
    • , Gerard Karsenty
    • , Young Seok Ju
    • , Chan Choi
    • , Jae Myoung Suh
    • , Jun Yong Park
    • , Sangkyu Park
    •  & Hail Kim
  • Article | | open

    CD8 T cells can protect the liver from viral infection, but can also result in severe liver damage and organ failure. Here, the authors develop a mouse model reflecting fulminant CD8 T cell mediated viral hepatitis, which occurs in a perforin-dependent manner that is protected by the use of perforin inhibitors.

    • M. Welz
    • , S. Eickhoff
    • , Z. Abdullah
    • , J. Trebicka
    • , K. H. Gartlan
    • , J. A. Spicer
    • , A. J. Demetris
    • , H. Akhlaghi
    • , M. Anton
    • , K. Manske
    • , D. Zehn
    • , B. Nieswandt
    • , C. Kurts
    • , J. A. Trapani
    • , P. Knolle
    • , D. Wohlleber
    •  & W. Kastenmüller
  • Article | | open

    Bacteriophages of the crAssphage family have not yet been isolated, despite being highly abundant in the human gut. Here, Shkoporov et al. isolate in pure culture one of these viruses and show that it infects the human gut symbiont Bacteroides intestinalis.

    • Andrey N. Shkoporov
    • , Ekaterina V. Khokhlova
    • , C. Brian Fitzgerald
    • , Stephen R. Stockdale
    • , Lorraine A. Draper
    • , R. Paul Ross
    •  & Colin Hill
  • Article | | open

    Colorectal cancers (CRCs) often develop into untreatable metastatic disease of the liver. Here the authors report the modification of extracellular matrix proteins by citrullination in CRC metastases to the liver and propose that inhibition of citrullination could serve as therapeutic avenue in the treatment.

    • A. E. Yuzhalin
    • , A. N. Gordon-Weeks
    • , M. L. Tognoli
    • , K. Jones
    • , B. Markelc
    • , R. Konietzny
    • , R. Fischer
    • , A. Muth
    • , E. O’Neill
    • , P. R. Thompson
    • , P. J. Venables
    • , B. M. Kessler
    • , S. Y. Lim
    •  & R. J. Muschel
  • Article | | open

    Ubiquitin-specific protease 14 (USP14) is a proteasome-associated deubiquitinating enzyme with known roles in physiology and disease. Here the authors show that fatty acid synthase (FASN) is a substrate of USP14, and that by stabilizing FASN, it plays a role in hepatosteatosis.

    • Bin Liu
    • , Shangwen Jiang
    • , Min Li
    • , Xuelian Xiong
    • , Mingrui Zhu
    • , Duanzhuo Li
    • , Lei Zhao
    • , Lili Qian
    • , Linhui Zhai
    • , Jing Li
    • , Han Lu
    • , Shengnan Sun
    • , Jiandie Lin
    • , Yan Lu
    • , Xiaoying Li
    •  & Minjia Tan
  • Article | | open

    Gluten-free diets are increasingly common in the general population. Here, the authors report the results of a randomised cross-over trial involving middle-aged, healthy Danish adults, showing evidence that a low-gluten diet leads to gut microbiome changes, possibly due to variations in dietary fibres.

    • Lea B. S. Hansen
    • , Henrik M. Roager
    • , Nadja B. Søndertoft
    • , Rikke J. Gøbel
    • , Mette Kristensen
    • , Mireia Vallès-Colomer
    • , Sara Vieira-Silva
    • , Sabine Ibrügger
    • , Mads V. Lind
    • , Rasmus B. Mærkedahl
    • , Martin I. Bahl
    • , Mia L. Madsen
    • , Jesper Havelund
    • , Gwen Falony
    • , Inge Tetens
    • , Trine Nielsen
    • , Kristine H. Allin
    • , Henrik L. Frandsen
    • , Bolette Hartmann
    • , Jens Juul Holst
    • , Morten H. Sparholt
    • , Jesper Holck
    • , Andreas Blennow
    • , Janne Marie Moll
    • , Anne S. Meyer
    • , Camilla Hoppe
    • , Jørgen H. Poulsen
    • , Vera Carvalho
    • , Domenico Sagnelli
    • , Marlene D. Dalgaard
    • , Anders F. Christensen
    • , Magnus Christian Lydolph
    • , Alastair B. Ross
    • , Silas Villas-Bôas
    • , Susanne Brix
    • , Thomas Sicheritz-Pontén
    • , Karsten Buschard
    • , Allan Linneberg
    • , Jüri J. Rumessen
    • , Claus T. Ekstrøm
    • , Christian Ritz
    • , Karsten Kristiansen
    • , H. Bjørn Nielsen
    • , Henrik Vestergaard
    • , Nils J. Færgeman
    • , Jeroen Raes
    • , Hanne Frøkiær
    • , Torben Hansen
    • , Lotte Lauritzen
    • , Ramneek Gupta
    • , Tine Rask Licht
    •  & Oluf Pedersen
  • Article | | open

    Excess caloric intake leads to increased thermogenesis in brown adipose tissue, to limit weight gain. Here, the authors show that neuropeptide FF receptor-2 signalling promotes thermogenesis via control of NPY expression in the arcuate nucleus, and that it absence in mice leads to a failure of activation of diet-induced thermogenesis and the development of exacerbated obesity.

    • Lei Zhang
    • , Chi Kin Ip
    • , I-Chieh J. Lee
    • , Yue Qi
    • , Felicia Reed
    • , Tim Karl
    • , Jac Kee Low
    • , Ronaldo F. Enriquez
    • , Nicola J. Lee
    • , Paul A. Baldock
    •  & Herbert Herzog
  • Article | | open

    Gut microbiota impact host metabolism and gut microbiome composition reflects dietary habits. Here the authors show that, in animals fed obesogenic diets, changes in gut microbiota precede changes in glucose homeostasis. Importantly, long term exposure of the host to the changed microbiota is required to impair glucose homeostasis.

    • Kevin P. Foley
    • , Soumaya Zlitni
    • , Emmanuel Denou
    • , Brittany M. Duggan
    • , Rebecca W. Chan
    • , Jennifer C. Stearns
    •  & Jonathan D. Schertzer
  • Article | | open

    Infants born to obese mothers have altered microbiome and increased risk of obesity and NAFLD. Here the authors establish causality by showing that maternal obesity-shaped infant gut microbiome induces macrophage dysfunction, inflammation, and diet-induced metabolic disease in germ-free mice.

    • Taylor K. Soderborg
    • , Sarah E. Clark
    • , Christopher E. Mulligan
    • , Rachel C. Janssen
    • , Lyndsey Babcock
    • , Diana Ir
    • , Dominick J. Lemas
    • , Linda K. Johnson
    • , Tiffany Weir
    • , Laurel L. Lenz
    • , Daniel N. Frank
    • , Teri L. Hernandez
    • , Kristine A. Kuhn
    • , Angelo D’Alessandro
    • , Linda A. Barbour
    • , Karim C. El Kasmi
    •  & Jacob E. Friedman
  • Article | | open

    Diffuse Gastric Cancer (DGC) is increasingly being considered separate to intestinal type gastric cancer; several fusions events have been reported as drivers of the disease but few of those have been subsequently validated. Here the authors perform RNA-seq on early-onset DGC patients who had not been treated with chemotherapy or radiation and identify a previously unknown fusion.

    • Hanna Yang
    • , Dongwan Hong
    • , Soo Young Cho
    • , Young Soo Park
    • , Woo Ri Ko
    • , Ju Hee Kim
    • , Hoon Hur
    • , Jongkeun Lee
    • , Su-Jin Kim
    • , Sun Young Kwon
    • , Jae-Hyuk Lee
    • , Do Youn Park
    • , Kyu Sang Song
    • , Heekyung Chang
    • , Min-Hee Ryu
    • , Kye Soo Cho
    • , Jeong Won Kang
    • , Myeong-Cherl Kook
    • , Nina Thiessen
    • , An He
    • , Andy Mungall
    • , Sang-Uk Han
    •  & Hark Kyun Kim
  • Article | | open

    The development of single cell RNA sequencing technologies has been instrumental in advancing our understanding of tissue biology. Here, MacParland et al. performed single cell RNA sequencing of human liver samples, and identify distinct populations of intrahepatic macrophages that may play specific roles in liver disease.

    • Sonya A. MacParland
    • , Jeff C. Liu
    • , Xue-Zhong Ma
    • , Brendan T. Innes
    • , Agata M. Bartczak
    • , Blair K. Gage
    • , Justin Manuel
    • , Nicholas Khuu
    • , Juan Echeverri
    • , Ivan Linares
    • , Rahul Gupta
    • , Michael L. Cheng
    • , Lewis Y. Liu
    • , Damra Camat
    • , Sai W. Chung
    • , Rebecca K. Seliga
    • , Zigong Shao
    • , Elizabeth Lee
    • , Shinichiro Ogawa
    • , Mina Ogawa
    • , Michael D. Wilson
    • , Jason E. Fish
    • , Markus Selzner
    • , Anand Ghanekar
    • , David Grant
    • , Paul Greig
    • , Gonzalo Sapisochin
    • , Nazia Selzner
    • , Neil Winegarden
    • , Oyedele Adeyi
    • , Gordon Keller
    • , Gary D. Bader
    •  & Ian D. McGilvray
  • Article | | open

    Hepatocyte nuclear factor 4 alpha (HNF4α) is regulated by different promoters to generate two isoforms, one of which functions as a tumor suppressor. Here, the authors reveal that induction of the alternative isoform in hepatocellular carcinoma inhibits the circadian clock by repressing BMAL1, and the reintroduction of BMAL1 prevents HCC tumor growth.

    • Baharan Fekry
    • , Aleix Ribas-Latre
    • , Corrine Baumgartner
    • , Jonathan R. Deans
    • , Christopher Kwok
    • , Pooja Patel
    • , Loning Fu
    • , Rebecca Berdeaux
    • , Kai Sun
    • , Mikhail G. Kolonin
    • , Sidney H. Wang
    • , Seung-Hee Yoo
    • , Frances M. Sladek
    •  & Kristin Eckel-Mahan
  • Article | | open

    Barrett’s oesophagus is associated with an increased risk of oseophageal cancer, but its cell of origin is unclear. Here the authors show, using single-cell RNA sequencing of biopsies from six patients and two unaffected subjects, that cells in Barrett’s oesophagus show a transcriptional profile that is similar to that of cells in oesophageal submucosal glands.

    • Richard Peter Owen
    • , Michael Joseph White
    • , David Tyler Severson
    • , Barbara Braden
    • , Adam Bailey
    • , Robert Goldin
    • , Lai Mun Wang
    • , Carlos Ruiz-Puig
    • , Nicholas David Maynard
    • , Angie Green
    • , Paolo Piazza
    • , David Buck
    • , Mark Ross Middleton
    • , Chris Paul Ponting
    • , Benjamin Schuster-Böckler
    •  & Xin Lu
  • Article | | open

    Inflammatory bowel disease is characterised by epithelial dysfunction. Here the authors show that loss of the nuclear receptor LRH-1 leads to epithelial disruption by altering Notch signaling in mouse intestinal organoids, and that LRH-1 overexpression ameliorates immune-mediated colitis in a mouse model.

    • James R. Bayrer
    • , Hongtao Wang
    • , Roy Nattiv
    • , Miyuki Suzawa
    • , Hazel S. Escusa
    • , Robert J. Fletterick
    • , Ophir D. Klein
    • , David D. Moore
    •  & Holly A. Ingraham
  • Article | | open

    Studies on the effects of breastfeeding on the infant gut microbiota have provided inconsistent results. Here, Ho et al. perform a meta-analysis of seven studies across different populations, supporting that exclusive breastfeeding is associated with short-term and long-term alterations in the infant gut microbiota.

    • Nhan T. Ho
    • , Fan Li
    • , Kathleen A. Lee-Sarwar
    • , Hein M. Tun
    • , Bryan P. Brown
    • , Pia S. Pannaraj
    • , Jeffrey M. Bender
    • , Meghan B. Azad
    • , Amanda L. Thompson
    • , Scott T. Weiss
    • , M. Andrea Azcarate-Peril
    • , Augusto A. Litonjua
    • , Anita L. Kozyrskyj
    • , Heather B. Jaspan
    • , Grace M. Aldrovandi
    •  & Louise Kuhn