A Diet-Microbial Metabolism Feedforward Loop Modulates Intestinal Stem Cell Renewal in the Stressed Gut

The authors showed that dietary raffinose metabolism to fructose couples stress-induced gut microbial remodeling to intestinal stem cells renewal and epithelial homeostasis.
[Nature Communications]
Hou, Y., Wei, W., Guan, X., Liu, Y., Bian, G., He, D., Fan, Q., Cai, X., Zhang, Y., Wang, G., Zheng, X., & Hao, H. (2021). A diet-microbial metabolism feedforward loop modulates intestinal stem cell renewal in the stressed gut. Nature Communications, 12(1), 271. https://doi.org/10.1038/s41467-020-20673-4 Cite
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CREPT Is Required for Murine Stem Cell Maintenance during Intestinal Regeneration

Scientists report that CREPT, a recently identified tumor-promoting protein, was required for the maintenance of murine intestinal stem cells. CREPT was preferably expressed in the crypts but not in the villi.
[Nature Communications]
Yang, L., Yang, H., Chu, Y., Song, Y., Ding, L., Zhu, B., Zhai, W., Wang, X., Kuang, Y., Ren, F., Jia, B., Wu, W., Ye, X., Wang, Y., & Chang, Z. (2021). CREPT is required for murine stem cell maintenance during intestinal regeneration. Nature Communications, 12(1), 270. https://doi.org/10.1038/s41467-020-20636-9 Cite
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Bach2 Deficiency Promotes Intestinal Epithelial Regeneration by Accelerating DNA Repair in Intestinal Stem Cells

Researchers found that Bach2 deficiency promotes intestinal epithelial cell proliferation during homeostasis. Moreover, genetic inactivation of Bach2 in mouse intestinal epithelium facilitated crypt regeneration after irradiation, resulting in a reduction in mortality.
[Stem Cell Reports]
Li, Y., Rao, X., Tang, P., Chen, S., Guo, Q., Fu, G., Pan, M., Liang, L., Yao, Y., Gao, X., Zhou, Y., Zhang, Z., Xu, X., Hu, W., Gao, J., & Hua, G. (2020). Bach2 Deficiency Promotes Intestinal Epithelial Regeneration by Accelerating DNA Repair in Intestinal Stem Cells. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.12.005 Cite
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The Epigenetic Regulator Mll1 Is Required for Wnt-Driven Intestinal Tumorigenesis and Cancer Stemness

Investigators identified the histone methyltransferase Mll1 as a regulator of Wnt-driven intestinal cancer. Mll1 is highly expressed in Lgr5+ stem cells and human colon carcinomas with increased nuclear β-catenin.
[Nature Communications]
Grinat, J., Heuberger, J., Vidal, R. O., Goveas, N., Kosel, F., Berenguer-Llergo, A., Kranz, A., Wulf-Goldenberg, A., Behrens, D., Melcher, B., Sauer, S., Vieth, M., Batlle, E., Stewart, A. F., & Birchmeier, W. (2020). The epigenetic regulator Mll1 is required for Wnt-driven intestinal tumorigenesis and cancer stemness. Nature Communications, 11(1), 6422. https://doi.org/10.1038/s41467-020-20222-z Cite
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Non-Canonical Wnt/PCP Signaling Regulates Intestinal Stem Cell Lineage Priming towards Enteroendocrine and Paneth Cell Fates

Scientists discovered non-canonical Wnt/planar cell polarity-activated intestinal stem cells that are primed towards the enteroendocrine or Paneth cell lineage.
[Nature Cell Biology]
Böttcher, A., Büttner, M., Tritschler, S., Sterr, M., Aliluev, A., Oppenländer, L., Burtscher, I., Sass, S., Irmler, M., Beckers, J., Ziegenhain, C., Enard, W., Schamberger, A. C., Verhamme, F. M., Eickelberg, O., Theis, F. J., & Lickert, H. (2021). Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates. Nature Cell Biology, 1–9. https://doi.org/10.1038/s41556-020-00617-2 Cite
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Evaluation of Tissue Stem Cell Derived Human Intestinal Organoids, a Physiologically Relevant Model to Evaluate Cytochrome P450 Induction in Gut

Matched human enteroid and colonoid lines, generated from ileal and colon biopsies from two donors, were cultured in extracellular matrix for three days, followed by a single 48h treatment with rifampin, omeprazole, CITCO and phenytoin at concentrations that induce target genes in hepatocytes.
[Drug Metabolism and Disposition]
Evaluation of tissue stem cell derived human intestinal organoids, a physiologically relevant model to evaluate cytochrome P450 induction in gut | Drug Metabolism & Disposition. (n.d.). Retrieved January 5, 2021, from https://dmd.aspetjournals.org/content/early/2020/12/21/dmd.120.000281 Cite
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Distinct Populations of Crypt-Associated Fibroblasts Act as Signaling Hubs to Control Colon Homeostasis

To describe the relevant cell populations in an unbiased manner, researchers carried out a single-cell transcriptome analysis of the adult murine colon, producing a high-quality atlas of matched colonic epithelium and mesenchyme.
[PLoS Biology]
Brügger, M. D., Valenta, T., Fazilaty, H., Hausmann, G., & Basler, K. (2020). Distinct populations of crypt-associated fibroblasts act as signaling hubs to control colon homeostasis. PLOS Biology, 18(12), e3001032. https://doi.org/10.1371/journal.pbio.3001032 Cite
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Extracellular Matrix Mechanical Properties and Regulation of the Intestinal Stem Cells: When Mechanics Control Fate

Scientists review colon extracellular matrix physical properties at physiological and pathological states and their bioengineered in vitro reproduction applications to intestinal stem cell studies.
[Cells]
Onfroy-Roy, L., Hamel, D., Foncy, J., Malaquin, L., & Ferrand, A. (2020). Extracellular Matrix Mechanical Properties and Regulation of the Intestinal Stem Cells: When Mechanics Control Fate. Cells, 9(12), 2629. https://doi.org/10.3390/cells9122629 Cite
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Depletion of Intestinal Stem Cell Niche Factors Contributes to the Alteration of Epithelial Differentiation in SAMP1/YitFcsJ Mice With Crohn Disease-Like Ileitis

Using the intestine of SAMP1/YitFcsJ mice aged 10 to 14 weeks, morphometric alterations in the crypt-villus architecture, intestinal stem cells, crypt cells, and differentiated cells; organoid formation capacity of intestinal crypts; and niche signaling pathways were analyzed and compared with those of age-matched control AKR/J mice.
[Inflammatory Bowel Diseases]
Lee, C., Hong, S. N., Kim, E. R., Chang, D. K., & Kim, Y.-H. (n.d.). Depletion of Intestinal Stem Cell Niche Factors Contributes to the Alteration of Epithelial Differentiation in SAMP1/YitFcsJ Mice With Crohn Disease-Like Ileitis. Inflammatory Bowel Diseases. https://doi.org/10.1093/ibd/izaa314 Cite
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The Hippo–YAP Signaling as Guardian in the Pool of Intestinal Stem Cells

Scientists summarize recent advances in understanding the correlation between Hippo–YAP signaling and intestinal homeostasis, repair, and tumorigenesis, focusing specifically on intestinal stem cell regulation.
[Biomedicines]
Seo, Y., Park, S.-Y., Kim, H.-S., & Nam, J.-S. (2020). The Hippo–YAP Signaling as Guardian in the Pool of Intestinal Stem Cells. Biomedicines, 8(12), 560. https://doi.org/10.3390/biomedicines8120560 Cite
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Unlike LGR4, LGR5 Potentiates Wnt–β-Catenin Signaling without Sequestering E3 Ligases

Scientists examined the mechanisms of action of LGR4 and LGR5 in parallel using coimmunoprecipitation, proximity ligation, competition binding, and time-resolved FRET assays in whole cells.
[Science Signaling]
Park, S., Wu, L., Tu, J., Yu, W., Toh, Y., Carmon, K. S., & Liu, Q. J. (2020). Unlike LGR4, LGR5 potentiates Wnt–β-catenin signaling without sequestering E3 ligases. Science Signaling, 13(660). https://doi.org/10.1126/scisignal.aaz4051 Cite
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