Intestinal Cell News Volume 2.18 | May 20 2016

A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis
The authors generated 55 colorectal tumor organoid lines from a range of histological subtypes and clinical stages, including rare subtypes. [Cell Stem Cell]
Abstract | Graphical Abstract

Defensive Mutualism Rescues NADPH Oxidase Inactivation in Gut Infection
Scientists generated mice with complete or epithelium-restricted deficiency in the obligatory NOX dimerization partner Cyba. Researchers discovered that NOX1 regulates DUOX2 expression in the intestinal epithelium, which magnified the epithelial reactive oxygen species-deficiency. [Cell Host Microbe]
Abstract | Graphical Abstract

ERK5 Signaling Rescues Intestinal Epithelial Turnover and Tumor Cell Proliferation upon ERK1/2 Abrogation
Scientists showed that loss of Erk1/2 in intestinal epithelial cells results in defects in nutrient absorption, epithelial cell migration and secretory cell differentiation. [Nat Commun] Full Article | Press Release

Programming of Intestinal Epithelial Differentiation by IL-33 Derived from Pericryptal Fibroblasts in Response to Systemic Infection
Investigators demonstrated an unexpected function of IL-33 as a regulator of epithelial barrier functions. Mice lacking IL-33 showed decreased Paneth cell numbers and lethal systemic infection in response to Salmonella typhimurium. [Cell Rep] Full Article | Graphical Abstract

Intestine-Specific Homeobox (ISX) Upregulates E2F1 Expression and Related Oncogenic Activities in HCC
Researchers found that ISX transcriptionally activated E2F transcription factor 1 (E2F1) and associated oncogenic activity by directly binding to the E2 site of its promoter. [Oncotarget] Full Article

Expression of an Oncogenic BARD1 Splice Variant Impairs Homologous Recombination and Predicts Response to PARP-1 Inhibitor Therapy in Colon Cancer
The authors showed that loss of BRCA1-associated RING domain protein 1 (BARD1) function through the expression of a BARD1 splice variant, BARD1β, results in a more malignant phenotype with decreased RAD51 foci formation, reduced BRCA1 E3 ubiquitin ligase activity, and decreased nuclear BRCA1 protein localization. BARD1β sensitizes colon cancer cells to poly ADP ribose polymerase 1 (PARP-1) inhibition even in a full-length BRCA1 background. [Sci Rep] Full Article

LPS Induces Hyper-Permeability of Intestinal Epithelial Cells
The authors elucidated the effect of lipopolysaccharides (LPS) on paracellular permeability known to be severely affected in necrotizing enterocoliti. [J Cell Physiol] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Notch Signaling Regulates Asymmetric Division and Inter-Conversion between Lgr5 and Bmi1 Expressing Intestinal Stem Cells
Rapidly cycling LGR5⁺ intestinal stem cells (ISCs) located at the base of crypts are the primary driver of regeneration. Additionally, BMI1 expression is correlated with a slow cycling pool of ISCs located at +4 position. Scientists provided evidence that NOTCH signaling regulates the balance between these two populations and promotes asymmetric division as a mechanism for interconversion in the mouse intestine. [Sci Rep] Full Article

β-Arrestin1 Inhibits Chemotherapy-Induced Intestinal Stem Cell Apoptosis and Mucositis
The authors demonstrated that chemotherapy induced intestinal mucositis by promoting crypt cell apoptosis, especially in Lgr5⁺ stem cells and Paneth cells but not in goblet cells, epithelial cells or vascular endothelial cells. [Cell Death Dis] Full Article

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RDD Pharma Announces First Patient Dosed in Phase III Clinical Trial for Chronic Anal Fissure
RDD Pharma announced that the first patient has been dosed in its Phase III clinical trial of RDD-1219 for the topical treatment of chronic anal fissure. [RDD Pharma (PR Newswire Association LLC.)] Press Release

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