ZNRF3 and RNF43 Cooperate to Safeguard Metabolic Liver Zonation and Hepatocyte Proliferation

Researchers showed that restricted chromatin accessibility in intestinal stem cells prevented the expression of β-Catenin-regulated metabolic enzymes, whereas fine-tuning of WNT/β-Catenin activity by ZNRF3 and RNF43 restricted proliferation in chromatin-permissive AXIN2+ hepatocytes, while preserving metabolic function.
[Cell Stem Cell]
Sun, T., Annunziato, S., Bergling, S., Sheng, C., Orsini, V., Forcella, P., Pikiolek, M., Kancherla, V., Holwerda, S., Imanci, D., Wu, F., Meylan, L. C., Puehringer, L. F., Waldt, A., Oertli, M., Schuierer, S., Terracciano, L. M., Reinker, S., Ruffner, H., … Tchorz, J. S. (2021). ZNRF3 and RNF43 cooperate to safeguard metabolic liver zonation and hepatocyte proliferation. Cell Stem Cell, 0(0). https://doi.org/10.1016/j.stem.2021.05.013 Cite
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The Phosphatase PRL-3 Affects Intestinal Homeostasis by Altering the Crypt Cell Composition

Researchers employed a doxycycline-inducible phosphatase of regenerating liver-3 (PRL-3) mouse strain to show that aberrant PRL-3 expression within a non-cancerous background led to the death of Lgr5+ intestinal stem cells and to Paneth cell expansion.
[Journal of Molecular Medicine]
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BCL-XL Is Crucial for Progression through the Adenoma-to-Carcinoma Sequence of Colorectal Cancer

By targeting antiapoptotic proteins with specific BH3 mimetics in organoid models of colorectal cancer progression, scientists found that BCL-2 was essential only during instestinal stem cell transformation while MCL1 inhibition did not affect adenoma outgrowth.
[Cell Death & Differentiation]
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Oncogenic BRAF, Unrestrained by TGFβ-Receptor Signaling, Drives Right-Sided Colonic Tumorigenesis

The proximal colonic tumors that developed in a mouse model of right-sided colon cancer exhibited a fetal-like progenitor phenotype (Ly6a/Sca1+) and lacked expression of Lgr5 and its associated intestinal stem cell signature.
[Nature Communications]
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High-Fat Diet-Activated Fatty Acid Oxidation Mediates Intestinal Stemness and Tumorigenicity

Scientists proposed that a high-fat diet enhanced intestinal stemness and tumorigenicity by engaging a peroxisome proliferator-activated receptor-fatty acid oxidation (PPAR-FAO) program.
[Cell Reports]
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RAL GTPases Mediate EGFR-Driven Intestinal Stem Cell Proliferation and Tumorigenesis

In addition to impacting stem cell proliferation during damage-induced intestinal regeneration, the role of RAL GTPases impacted on EGFR-dependent tumorigenic growth in the intestine and in human mammary epithelium.
[eLife]
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Apc-Mutant Cells Act as Supercompetitors in Intestinal Tumor Initiation

Investigators showed that Apc-mutant intestinal stem cells (ISCs) functioned as bona fide supercompetitors by secreting WNT antagonists, thereby inducing differentiation of neighbouring wild-type ISCs.
[Nature]
van Neerven, S. M., de Groot, N. E., Nijman, L. E., Scicluna, B. P., van Driel, M. S., Lecca, M. C., Warmerdam, D. O., Kakkar, V., Moreno, L. F., Vieira Braga, F. A., Sanches, D. R., Ramesh, P., ten Hoorn, S., Aelvoet, A. S., van Boxel, M. F., Koens, L., Krawczyk, P. M., Koster, J., Dekker, E., … Vermeulen, L. (2021). Apc-mutant cells act as supercompetitors in intestinal tumour initiation. Nature, 1–6. https://doi.org/10.1038/s41586-021-03558-4 Cite
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NOTUM from Apc-Mutant Cells Biases Clonal Competition to Initiate Cancer

Researchers investigated how Apc-mutant cells gain a clonal advantage over wild-type counterparts to achieve fixation and found that Apc-mutant cells were enriched for transcripts that encoded several secreted WNT antagonists, with Notum being the most highly expressed.
[Nature]
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cGAS Restricts Colon Cancer Development by Protecting Intestinal Barrier Integrity

Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) deficiency led to intestinal stem cell loss and compromised intestinal barrier integrity upon dextran sodium sulfate-induced acute injury.
[Proceedings of the National Academy of Sciences of the United States of America]
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Clinical Trial Launched Following Discovery That Psychiatric Drug May Prevent Bowel Cancer

Following successful research that showed how a drug available on the NHS could boost fitness of healthy stem cells in the gut, a clinical trial funded by the Dutch Cancer Society testing the effect of lithium of bowel cancer development in individuals with familial adenomatous polyposis will be performed in the Netherlands.
[Worldwide Cancer Research (EurekAlert!)]
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In Vitro Co-Culture of Human Intestinal Organoids and Lamina Propria-Derived CD4+ T Cells

Investigators provided a detailed protocol for an autologous in vitro long-term 3D co-culture system of human intestinal CD4+ T cells and intestinal stem cells to study T cell-intestinal epithelial cell interactions during tissue development and inflammation.
[STAR Protocols]
Schreurs, R. R. C. E., Baumdick, M. E., Drewniak, A., & Bunders, M. J. (2021). In vitro co-culture of human intestinal organoids and lamina propria-derived CD4+ T cells. STAR Protocols, 2(2), 100519. https://doi.org/10.1016/j.xpro.2021.100519 Cite
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