Investigators optimized and characterized rat duodenal organoids with light and electron microscopy, immunofluorescence and notably, global mRNA expression.
6445218 HSLMIWEB items 1 apa default asc 1
Hedrich, W. D., Panzica-Kelly, J. M., Chen, S.-J., Strassle, B., Hasson, C., Lecureux, L., Wang, L., Chen, W., Sherry, T., Gan, J., & Davis, M. (2020). Development and characterization of rat duodenal organoids for ADME and toxicology applications. Toxicology, 152614. https://doi.org/10.1016/j.tox.2020.152614 Cite
Bmi1-specific Klf4 deletion resulted in decreased numbers of MSI1+ cells in regenerating crypts compared to those of control mice. Researchers showed that KLF4 bound to the Msi1 promoter and activated its expression in vitro.
6445218 URWQ86V7 items 1 apa default asc 1
Interplay among p21 Waf1/Cip1 , MUSASHI-1 and Krüppel-like factor 4 in activation of Bmi1-Cre ER reserve intestinal stem cells after gamma radiation-induced injury | Scientific Reports. (n.d.). Retrieved October 27, 2020, from https://www.nature.com/articles/s41598-020-75171-w Cite
Scientists utilized mice and small intestinal organoid models to clarify the role of L-arginine on epithelial differentiation of intestinal stem cells (ISCs). They showed that L-arginine increased expansion of ISCs in mice.
6445218 8BV3ZHKM items 1 apa default asc 1
Hou, Q., Dong, Y., Huang, J., Liao, C., Lei, J., Wang, Y., Lai, Y., Bian, Y., He, Y., Sun, J., Sun, M., Jiang, Q., Wang, B., Yu, Z., Guo, Y., & Zhang, B. (2020). Exogenous L-arginine increases intestinal stem cell function through CD90+ stromal cells producing mTORC1-induced Wnt2b. Communications Biology, 3(1), 1–16. https://doi.org/10.1038/s42003-020-01347-9 Cite
Dysregulation of intestinal epithelial cells(IEC) homeostasis likely contributes to the development of intestinal inflammation and intestinal cancer. The roles of receptor protein tyrosine kinases and their downstream signaling molecules such as Src family kinases, Ras, and mammalian target of rapamycin in homeostatic regulation of IEC turnover have recently been evaluated.
Using novel Paneth cell-specific IL-22Ra1 knockout mice, researchers showed that IL-22 signaling in Paneth cells was required for small intestinal host defense. They showed that Paneth cell maturation, antimicrobial effector function, expression of specific WNTs, and organoid morphogenesis were dependent on cell-intrinsic IL-22Ra1 signaling.
6445218 PHJKG385 items 1 apa default asc 1
Gaudino, S. J., Beaupre, M., Lin, X., Joshi, P., Rathi, S., McLaughlin, P. A., Kempen, C., Mehta, N., Eskiocak, O., Yueh, B., Blumberg, R. S., van der Velden, A. W. M., Shroyer, K. R., Bialkowska, A. B., Beyaz, S., & Kumar, P. (2020). IL-22 receptor signaling in Paneth cells is critical for their maturation, microbiota colonization, Th17-related immune responses, and anti- Salmonella immunity. Mucosal Immunology, 1–13. https://doi.org/10.1038/s41385-020-00348-5 Cite
Researchers showed that volumetric compression regulated the growth of intestinal organoids by modifying intracellular crowding and elevating Wnt/β-catenin signaling.
[Cell Stem Cell]
6445218 DXKLZAJB items 1 apa default asc 1
By combining quantitative imaging with RNA sequencing, scientists showed the role of endogenous retinoic acid metabolism in initiating transcriptional programs that guide the cell-fate transitions of intestinal epithelium, and identified an inhibitor of the retinoid X receptor that improves intestinal regeneration in vivo.
6606345 T799XBL3 items 1 apa default asc 1
Lukonin, I., Serra, D., Challet Meylan, L., Volkmann, K., Baaten, J., Zhao, R., Meeusen, S., Colman, K., Maurer, F., Stadler, M. B., Jenkins, J., & Liberali, P. (2020). Phenotypic landscape of intestinal organoid regeneration. Nature, 586(7828), 275–280. https://doi.org/10.1038/s41586-020-2776-9 Cite
Recent studies investigating the role of MHC class II+ exosomes released by Intestinal epithelial cells report conflicting findings of either immune enhancing or immunosuppressive activities. In addition to modulating inflammatory responses, recent findings suggest that MHC class II expression by intestinal stem cells may elicit crosstalk that promotes epithelial renewal.
Investigators showed that both normal crypts and tumors underwent metabolic remodeling in response to oxidative phosphorylation deficiency by upregulating the de novo serine synthesis pathway.
6606345 X93VBF73 items 1 apa default asc 1
Smith, A. L. M., Whitehall, J. C., Bradshaw, C., Gay, D., Robertson, F., Blain, A. P., Hudson, G., Pyle, A., Houghton, D., Hunt, M., Sampson, J. N., Stamp, C., Mallett, G., Amarnath, S., Leslie, J., Oakley, F., Wilson, L., Baker, A., Russell, O. M., … Greaves, L. C. (2020). Age-associated mitochondrial DNA mutations cause metabolic remodeling that contributes to accelerated intestinal tumorigenesis. Nature Cancer, 1–14. https://doi.org/10.1038/s43018-020-00112-5 Cite
Recent discoveries have revealed that the lineage plasticity of committed cells — combined with redundant sources of niche signals — enables the epithelium to efficiently repair tissue damage. New approaches such as single-cell transcriptomics and the use of organoid models have led to the identification of the signals that guide fate specification of stem cell progeny into the six intestinal cell lineages. These cell types display context-dependent functionality and can adapt to different requirements over their lifetime, as dictated by their microenvironment.
[Nature Reviews Molecular Cell Biology]
While Ubc9+/− mice displayed no overt phenotypes and no globally visible hyposumoylation in cells of the small intestine, scientists found that, upon loss of Apc in both models, Ubc9+/− mice developed more intestinal adenomas and showed significantly shortened survival. This was accompanied by reduced global sumoylation levels in the polyps, indicating that Ubc9 levels became critical upon oncogenic stress.
6606345 I56K4ULZ items 1 apa default asc 1
An unanticipated tumor-suppressive role of the SUMO pathway in the intestine unveiled by Ubc9 haploinsufficiency | Oncogene. (n.d.). Retrieved September 18, 2020, from https://www.nature.com/articles/s41388-020-01457-y Cite