Intestinal Cell News Volume 6.06 | Feb 21 2020

TOP STORY

Cell-Type-Specific Signaling Networks in Heterocellular Organoids

Simultaneous analysis by mass cytometry of 28 post-translational modifications in >1 million single cells derived from small intestinal organoids revealed cell-type- and cell-state-specific signaling networks in stem, Paneth, enteroendocrine, tuft and goblet cells, as well as enterocytes. [Nat Methods] Abstract | Press Release

(Ranked by impact factor of the journal)

CRISPR-Based Adenine Editors Correct Nonsense Mutations in a Cystic Fibrosis Organoid Biobank

Researchers describe a cystic fibrosis (CF) intestinal organoid biobank, representing 664 patients, of which ~20% could theoretically be repaired by adenine base editing (ABE). They applied SpCas9-ABE and xCas9-ABE on four selected CF organoid samples. [Cell Stem Cell] Abstract | Graphical Abstract

Ascl2-Dependent Cell Dedifferentiation Drives Regeneration of Ablated Intestinal Stem Cells

By timing the interval between LGR5⁺ lineage tracing and lethal injury, scientists showed that intestinal stem cell regeneration was explained nearly completely by dedifferentiation, with contributions from absorptive and secretory progenitors. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release

miR-4711-5p Regulates Cancer Stemness and Cell Cycle Progression via KLF5, MDM2 and TFDP1 in Colon Cancer Cells

Investigators identified one promising miRNA, miR-4711-5p, that downregulated Kruppel-like factor 5 (KLF5) expression by direct binding. This miRNA suppressed cell proliferation, migration and invasion ability, as well as stemness, including decreased stem cell marker expression, reactive oxygen species activity and sphere formation ability. [Br J Cancer] Abstract

New Role of the Antidepressant Imipramine as a Fascin1 Inhibitor in Colorectal Cancer Cells

Assays investigating lamellipodia formation and migration and invasion of colorectal cancer cells in vitro using 3D human tissue demonstrated anti-fascin1 and anti-invasive activities of imipramine. [Exp Mol Med] Full Article

Germ‐Free and Microbiota‐Associated Mice Yield Small Intestinal Epithelial Organoids with Equivalent and Robust Transcriptome/Proteome Expression Phenotypes

The authors probed the effect of donor microbiota differences, previously identified as a confounding factor in murine in vivo studies, on organoids. They analyzed the proteomes and transcriptomes of primary organoid cultures established from two colonized and one germ‐free mouse colony of C57BL/6J genetic background, and compared them to their tissue of origin and commonly used cell lines. [Cell Microbiol] Abstract

APC Controls Wnt-Induced β-Catenin Destruction Complex Recruitment in Human Colonocytes

Researchers utilized Wnt3a-beads to locally activate Wnt co-receptors. In response, the endogenous β-catenin destruction complex reoriented toward the local Wnt cue in colorectal cancer cells with full-length Adenomatous Polyposis Coli (APC), but not if APC was truncated or depleted. [Sci Rep] Full Article

Transcytosis of Bacillus subtilis Extracellular Vesicles through an In Vitro Intestinal Epithelial Cell Model

Using confocal laser scanning microscopy, the authors report that uptake and internalization of CFSE-labeled B. subtilis EVs by Caco-2 cells were time-dependent. [Sci Rep] Full Article

Matrine Triggers Colon Cancer Cell Apoptosis and G0/G1 Cell Cycle Arrest via Mediation of MicroRNA‐22

Matrine (MAT) prohibited cell viability, accelerated apoptosis, and triggered cells cycle stagnation at the G0/G1 phase. Additionally, miR‐22 was elevated by MAT; meanwhile, the influences of MAT were all inverted by miR‐22 inhibitor. [Phytother Res] Abstract

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Crosstalk among Colon Cancer-Derived Exosomes, Fibroblast-Derived Exosomes, and Macrophage Phenotypes in Colon Cancer Metastasis

The authors highlight the crosstalk among colon cancer-derived exosomes, macrophage phenotypes and fibroblasts during colon cancer metastasis. [Int Immunopharmacol] Abstract

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CytoDyn Receives Institutional Review Board Approval to Initiate Phase II Basket Trial for 22 Solid Tumor Cancers

CytoDyn, Inc. reported that it has received Institutional Review Board approval to begin its Phase II clinical trial for the treatment of approximately 22 different solid tumor cancers, including melanoma, brain-glioblastoma, throat, lung, stomach, colon carcinoma, breast, testicular, ovarian, uterine, pancreas, bladder, among other indications. [CytoDyn, Inc.] Press Release

Innovation Pharmaceuticals Phase I Trial of Brilacidin for Ulcerative Colitis Meets Primary Endpoints; Positive Topline Results of Oral Brilacidin

Innovation Pharmaceuticals, Inc. announced that preliminary top-line data from its Phase I trial studying the use of delayed-release tablets of Brilacidin showed the trial met its primary endpoints. [Innovation Pharmaceuticals, Inc.] Press Release

Has the UK Science Minister Been Demoted?

A government reshuffle in the United Kingdom has born another new science minister – a position that has seen a revolving door of appointees, firings and resignations in recent years. The latest appointment also comes with an apparent political demotion for the role, which expert observers say is in conflict with a government that appears to have put research and innovation at the heart of its agenda. [Nature News] Editorial

NIH Hosts Nonhuman Primate Workshop Amidst Increased Scrutiny of Monkey Research

More than three years after it hosted a workshop on the science and ethics of biomedical studies on monkeys, the National Institutes of Health (NIH) this week convened another workshop on nonhuman primate research. And much like the previous event, the meeting is drawing sharply divergent reactions from biomedical and animal advocacy groups. [ScienceInsider] Editorial

Animal Welfare Records Return to USDA Website

On February 18, the US Department of Agriculture replaced on its website the animal welfare records that the agency had removed in early 2017 and added records that had been generated since, as ordered by Congress, The Washington Post reports. These documents, unredacted and searchable, include thousands of reports from unannounced inspections at research labs as well as zoos, circuses, dog breeders, and other facilities. [The Scientist] Editorial

White House Formally Invites Public Comment on Open-Access Policies

The White House issued a notice seeking comment on its effort to enhance public access to federally funded research. It’s an old idea creating new controversy. White House Office of Science and Technology Policy Director Kelvin Droegemeier is pushing back against publishers that in December said the administration was quietly pursuing an executive order to require immediate free distribution of taxpayer funded research. [ScienceInsider] Editorial

NEW Tissue Stem Cell Regulation by Autonomous and Non-Autonomous Mechanisms
July 12-17, 2020
Ventura, California, United States

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NEW Postdoctoral Fellow Position – Gene Editing and Genomic Evolution (Northwestern University)

NEW Postdoctoral Position – Intestinal Microbiology and Ecology (Technical University of Denmark)

NEW Assistant Professor – Food, Nutrition and Gastrointestinal Health (Wageningen University & Research Centre)

Postdoctoral Position – Inflammatory Bowel Disease (University of Copenhagen)

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

Postdoctoral Position – Intestinal Immunity (The University of Chicago)

Postdoctoral Associate – Intestinal Immunology (The Scripps Research Institute)

Postdoctoral Position – Epigenetic Control by the Novel Histone Methyltransferase KMT9 (University of Freiburg)

Research Scientist – In Vivo Research on Wnt Signaling in Self-Renewal (Surrozen)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

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