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| http://dx.doi.org/10.1136/gut.36.3.321 | DOI Listing |
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Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning.
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Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Intestinal epithelial cells are segregated into proliferative crypts and differentiated regions. This organization relies on specific signals, including Wnt3a, which regulates cell proliferation within crypts, and Eph/Ephrin, which dictates cell positioning along the crypt-villus axis. However, studying how the spatial distributions of these signals influences crypt-villus organization is challenging both in vitro and in vivo.
View Article and Find Full Text PDFNicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway.
Elife
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Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited.
View Article and Find Full Text PDFA tunable human intestinal organoid system achieves controlled balance between self-renewal and differentiation.
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Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
A balance between stem cell self-renewal and differentiation is required to maintain concurrent proliferation and cellular diversification in organoids; however, this has proven difficult in homogeneous cultures devoid of in vivo spatial niche gradients for adult stem cell-derived organoids. In this study, we leverage a combination of small molecule pathway modulators to enhance the stemness of organoid stem cells, thereby amplifying their differentiation potential and subsequently increasing cellular diversity within human intestinal organoids without the need for artificial spatial or temporal signaling gradients. Moreover, we demonstrate that this balance between self-renewal and differentiation can be effectively and reversibly shifted from secretory cell differentiation to the enterocyte lineage with enhanced proliferation using BET inhibitors, or unidirectional differentiation towards specific intestinal cell types by manipulating in vivo niche signals such as Wnt, Notch, and BMP.
View Article and Find Full Text PDFEnterocyte-like differentiation defines metabolic gene signatures of CMS3 colorectal cancers and provides therapeutic vulnerability.
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Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Colorectal cancer (CRC) is stratified into four consensus molecular subtypes (CMS1-4). CMS3 represents the metabolic subtype, but its wiring remains largely undefined. To identify the underlying tumorigenesis of CMS3, organoids derived from 16 genetically engineered mouse models are analyzed.
View Article and Find Full Text PDFSTAT1 regulates immune-mediated intestinal stem cell proliferation and epithelial regeneration.
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Department of Medicine and Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
The role of the immune system in regulating tissue stem cells remains poorly understood, as does the relationship between immune-mediated tissue damage and regeneration. Graft vs. host disease (GVHD) occurring after allogeneic bone marrow transplantation (allo-BMT) involves immune-mediated damage to the intestinal epithelium and its stem cell compartment.
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