Intestinal stem cell (ISC)-specific inhibition of white suppressed aging-induced ISC dysregulation and prolonged lifespan.
Elevation of Cdc42 activity in young animals by genetic means causes premature ISC aging, whereas pharmacological suppression of elevated Cdc42 activity restores organoid formation potential in vitro.
By using ex vivo 3D organoid cultures and molecular approaches scientists observed early responses to T3 involving the T3-metabolizing enzyme Dio1 and the transporter Mct10, accompanied by a complex response of stem cell- and progenitor-enriched genes.
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Godart, M., Frau, C., Farhat, D., Giolito, M. V., Jamard, C., Nevé, C. L., Freund, J.-N., Penalva, L. O., Sirakov, M., & Plateroti, M. (2021). The murine intestinal stem cells are highly sensitive to the modulation of the T3/TRα1-dependent pathway. Development. https://doi.org/10.1242/dev.194357 Cite
Combined bulk transcriptomic and single-cell RNA-sequencing analysis revealed decreased gene expression of markers for differentiated cells in patient-derived organoids derived from metastatic lesions.
[Stem Cell Reports]
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Okamoto, T., duVerle, D., Yaginuma, K., Natsume, Y., Yamanaka, H., Kusama, D., Fukuda, M., Yamamoto, M., Perraudeau, F., Srivastava, U., Kashima, Y., Suzuki, A., Kuze, Y., Takahashi, Y., Ueno, M., Sakai, Y., Noda, T., Tsuda, K., Suzuki, Y., … Yao, R. (2021). Comparative Analysis of Patient-Matched PDOs Revealed a Reduction in OLFM4-Associated Clusters in Metastatic Lesions in Colorectal Cancer. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2021.02.012 Cite
Scientists summarize the signaling pathways contributing to intestinal cell fates and homeostasis functions, focusing on intestinal stem cell proliferation, cell junction formation, remodeling, hypoxia, the impact of intestinal microbiota, the immune system, inflammation, and metabolism.
[Cell Communication and Signaling]
To determine the physiological role of MAP3K2-regulated intestinal stromal cells (MRISCs), scientists co-cultured MRISCs with colonic organoids and found that organoid growth was greater than when co-cultured with MRISC-depleted stromal cells
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Wu, N., Sun, H., Zhao, X., Zhang, Y., Tan, J., Qi, Y., Wang, Q., Ng, M., Liu, Z., He, L., Niu, X., Chen, L., Liu, Z., Li, H.-B., Zeng, Y. A., Roulis, M., Liu, D., Cheng, J., Zhou, B., … Su, B. (2021). MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche. Nature, 1–5. https://doi.org/10.1038/s41586-021-03283-y Cite
In colitis crypts, a notable cytokine–cytokine receptor, miR-494-3p-targeted EDA2R and the ligand EDA-A2, suppressed colonic stemness and epithelial repair by inhibiting β-catenin/c-Myc. In differentiated intestinal epithelial cells, miR-494-3p inhibited macrophage recruitment, M1 activation and EDA-A2 secretion by targeting IKKβ/NF-κB in colitis.
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Studies on the role of farnesoid X receptor in metabolic diseases and gastrointestinal and liver cancer are discussed, and the potential for development of targeted drugs are summarized.
[Nature Reviews Gastroenterology & Hepatology]
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Human intestinal stem cell-derived enteroids did not support virus replication from every HuNoV-positive stool sample, which led the authors to test and optimize new medium conditions, identify characteristics of stool samples that allow replication, and evaluate consistency of replication over time.
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Using a Lgr5-2A-DTR model, which ablates Lgr5+ cells with near-complete efficiency and retains endogenous levels of Lgr5 expression, researchers showed that persistent depletion of Lgr5+ intestinal stem cells in fact compromised small intestinal epithelial integrity and reduced epithelial turnover in vivo.
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The authors showed that dietary raffinose metabolism to fructose couples stress-induced gut microbial remodeling to intestinal stem cells renewal and epithelial homeostasis.
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