Intestinal Cell News Volume 4.00 | Jan 5 2018

TOP STORY

mTORC1 Inactivation Promotes Colitis-Induced Colorectal Cancer but Protects from APC Loss-Dependent Tumorigenesis

The authors showed that mTORC1 inactivation-induced chromosomal instability impairs intestinal crypt proliferation and regeneration, CDK4/6 dependently. [Cell Metab] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Reconstruction of the Human Colon Epithelium In Vivo

Researchers established an orthotopic xenograft system for normal human colon organoids, enabling stable reconstruction of the human colon epithelium in vivo. [Cell Stem Cell] Abstract | Graphical Abstract

Degree of Tissue Differentiation Dictates Susceptibility to BRAF-Driven Colorectal Cancer

Scientists found that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient in BRAF-driven mouse models of colon cancer. [Cell Rep] Full Article | Graphical Abstract

T-Bet-Independent Th1 Response Induces Intestinal Immunopathology during Toxoplasma gondii Infection

The investigation of the lymphoid cell-specific contribution to the IFN-γ-mediated intestinal pathology during T. gondii infection identified CD4⁺ T cells as a key cell population responsible for IFN-γ-dependent intestinal inflammation and Paneth cell loss, where T-bet-dependent group 1 innate lymphoid cells have a minor role in driving the parasite-induced immunopathology. [Mucosal Immunol] Abstract

A Phyllopod-Mediated Feedback Loop Promotes Intestinal Stem Cell Enteroendocrine Commitment in Drosophila

Researchers identified Phyllopod (Phyl) as a key regulator that drives enteroendocrine cells generation from intestinal stem cells. Phyl, which is normally suppressed by Notch, functions as an adaptor protein that bridges Tramtrack 69 and E3 ubiquitin ligase Sina for degradation. [Stem Cell Reports] Full Article | Graphical Abstract

JAK/STAT-1 Signaling Is Required for Reserve Intestinal Stem Cell Activation during Intestinal Regeneration following Acute Inflammation

Scientists investigated the impact of inflammation on intestinal stem cell (ISC) behavior during the regenerative response. In a murine model of αCD3 antibody-induced small-intestinal inflammation, reserve-ISCs proved highly resistant to injury, while crypt base columnar ISCs underwent apoptosis. [Stem Cell Reports] Full Article | Graphical Abstract

miR-145 Antagonizes SNAI1-Mediated Stemness and Radiation Resistance in Colorectal Cancer

Stable expression of SNAI1 in DLD1 and HCT116 cells increased expression of Nanog and decreased miR-145 expression compared to control cells. Using a miR-145 luciferase reporter assay, the authors determined that ectopic SNAI1 expression significantly repressed the miR-145 promoter. [Mol Ther] Abstract

Consensus Molecular Subtypes of Colorectal Cancer Are Recapitulated in In Vitro and In Vivo Models

Scientists determined the heterogeneity and identify the presence of consensus molecular subtypes in a large panel of colorectal cancer cell lines, primary cultures and patient-derived xenografts. [Cell Death Differ] Abstract

Development of Arrayed Colonic Organoids for Screening of Secretagogues Associated with Enterotoxins

An analytical platform with colonic organoids localized to the planar surface of a hydrogel layer was developed. The arrays of densely-packed colonoids were generated in a 96-well plate enabling assay of the response of hundreds of organoids so that organoid subpopulations with distinct behaviors were identifiable. [Anal Chem] Abstract

shRNA-Induced Silencing of Ras-Related C3 Botulinum Toxin Substrate 1 Inhibits the Proliferation of Colon Cancer Cells through Upregulation of BAD and Downregulation of Cyclin D1

Researchers investigated the effects of ras-related C3 botulinum toxin substrate 1 (RAC1) knockdown on cell proliferation, cell cycle progression and apoptosis of colon cancer cells. Lentivirus-mediated short hairpin RNA (shRNA) was used to knockdown RAC1 expression in colon cancer cell lines, and cell proliferation, apoptosis, cell cycle progression were evaluated by MTT assays and flow cytometry. [Int J Mol Med] Abstract

A Retroviral Replicating Vector Encoding Cytosine Deaminase and 5-FC Induces Immune Memory in Metastatic Colorectal Cancer Models

Intravenous delivery of Toca 511 resulted in substantial tumor-selective uptake of vector into metastatic lesions. Subsequent treatment with 5-fluorocytosine (5-FC) resulted in tumor shrinkage, improved survival, and immune memory against future rechallenge with the same CT26 colorectal carcinoma cell line. [Mol Ther Oncolytics] Full Article

Regenerating Human Epithelia with Cultured Stem Cells: Feeder Cells, Organoids and Beyond

Scientists outline the history of stratified epithelial stem cell culture and the application of cultured epithelial cells in clinical therapies. They further discuss the derivation of organoids from other types of epithelia and the challenges that remain for the translation of novel stem cell therapies toward clinical use. [EMBO Mol Med] Full Article

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Takeda and TiGenix Announce that Cx601 (Darvadstrocel) Has Received a Positive CHMP Opinion to Treat Complex Perianal Fistulas in Crohn’s Disease

Takeda Pharmaceutical Company Limited and TiGenix NV announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency, in conjunction with the Committee for Advanced Therapies, has adopted a positive opinion recommending a marketing authorization for investigational compound Cx601. [Takeda Pharmaceutical Company Limited] Press Release

Takeda Announces Intention to Acquire TiGenix

Takeda Pharmaceutical Company Limited announced its intention to acquire TiGenix NV and as a result has entered into an offer and support agreement with TiGenix which provides for a recommended potential voluntary public takeover bid for TiGenix. [Takeda Pharmaceutical Company Limited] Press Release

Germany vs Elsevier: Universities Win Temporary Journal Access after Refusing to Pay Fees

The Dutch publishing giant Elsevier has granted uninterrupted access to its paywalled journals for researchers at around 200 German universities and research institutes that had refused to renew their individual subscriptions at the end of 2017. [Nature News] Editorial

Nobel Laureate Will Step Down from Leading Embattled Salk Institute

Elizabeth Blackburn, the Nobel Prize–winning molecular biologist who took over just two years ago as president of the Salk Institute for Biological Studies in San Diego, California, announced her intent to retire this summer. The unexpected news comes as Salk faces gender discrimination lawsuits from three veteran female scientists and Blackburn herself has been challenged for not moving quickly enough to change what one plaintiff’s suit called an “old boys club” at the renowned research institute. [ScienceInsider] Editorial

Chile Election Reignites Tussle over Science Policy

Chile’s new President-elect Sebastián Piñera is poised to reshape science policy in the country. His plans to forge closer ties among science, education and industry have sparked enthusiasm from scientists who hope the plan will bolster support for their work — but also concern about possible changes in research priorities. [Nature News] Editorial

NEW MDI Biological Laboratory: Applications of Organoid Technology
May 27-June 2, 2018
Bar Harbor, Maine, United States

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NEW Postdoctoral Position – Intestinal Research (University of Pennsylvania)

NEW Research Technician – Translational Cell Assays (Karolinska Institutet)

NEW PhD Studentship – Molecular Probes for Imaging Lysyl Oxidase with Potential Application to the Detection of Metastasis (CRUK Manchester Institute)

NEW Postdoctoral Research Scientist – Liver-Gut Interaction (Quadram Institute)

NEW Postdoctoral Fellowship – Mouse Tumor Biology (Canadian Nuclear Laboratories)

Faculty Positions – Stem Cell & Organoid Medicine (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Fellow – Immunology (Icahn School of Medicine at Mount Sinai)

PhD Student – Stem Cells of the Intestine and the Stomach (German Cancer Research Center)

Postdoctoral Fellow – Modeling Physical Processes Underlying Digestion (Massey University)

PhD Studentships – MRC WIMM Prize (University of Oxford)

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