ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Inhibition of Notch signaling reduces the number of surviving Dclk1+ reserve crypt epithelial stem cells following radiation injury.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Phosphatidylinositol 3-Kinase Signaling Enhances Intestinal Crypt Epithelial Cell Recovery after Radiation.The American journal of pathology · 2025Article
- Balancing Regeneration and Resistance: Targeting DCLK1 to Mitigate Gastrointestinal Radiation Injury and Oncogenesis.Cancers · 2025Review
- Pathways regulating intestinal stem cells and potential therapeutic targets for radiation enteropathy.Molecular biomedicine · 2024Review
- Structure-Guided Prediction of the Functional Impact of DCLK1 Mutations on Tumorigenesis.Biomedicines · 2023Review
- The role of the Notch signalling pathway in the pathogenesis of ulcerative colitis: from the perspective of intestinal mucosal barrier.Frontiers in medicine · 2023Review
- The role of intestinal stem cell within gut homeostasis: Focusing on its interplay with gut microbiota and the regulating pathways.International journal of biological sciences · 2022Review
- DCLK1 isoforms and aberrant Notch signaling in the regulation of human and murine colitis.Cell death discovery · 2021Article
- The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways.Cancers · 2021Review
- Doublecortin-Like Kinase 1 (DCLK1) Is a Novel NOTCH Pathway Signaling Regulator in Head and Neck Squamous Cell Carcinoma.Frontiers in oncology · 2021Article
- Chemical Biology Toolkit for DCLK1 Reveals Connection to RNA Processing.Cell chemical biology · 2020Article
- Giant group I intron in a mitochondrial genome is removed by RNA back-splicing.BMC molecular biology · 2019Article
- Cellular Plasticity of Defa4Cellular and molecular gastroenterology and hepatology · 2019Article
- The GS-nitroxide JP4-039 improves intestinal barrier and stem cell recovery in irradiated mice.Scientific reports · 2018Article
- Role of ADAM10 in intestinal crypt homeostasis and tumorigenesis.Biochimica et biophysica acta. Molecular cell research · 2017Review
- Roles of Wnt Target Genes in the Journey of Cancer Stem Cells.International journal of molecular sciences · 2017Review
- 12-O-tetradecanoylphorbol-13-acetate (TPA) increases murine intestinal crypt stem cell survival following radiation injury.Oncotarget · 2017Article
- APSA Awardee Submission: Tumor/cancer stem cell marker doublecortin-like kinase 1 in liver diseases.Experimental biology and medicine (Maywood, N.J.) · 2017Review
- The Role of Intestinal Stem Cells in Epithelial Regeneration Following Radiation-Induced Gut Injury.Current stem cell reports · 2017Review
- Intestinal tuft cells regulate the ATM mediated DNA Damage response via Dclk1 dependent mechanism for crypt restitution following radiation injury.Scientific reports · 2016Article
- Use of biomarkers for assessing radiation injury and efficacy of countermeasures.Expert review of molecular diagnostics · 2016Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
We have previously reported that doublecortin-like kinase 1 (Dclk1) is a putative intestinal stem cell (ISC) marker. In this report, we evaluated the use of Dclk1 as a marker of surviving ISCs in response to treatment with high-dose total body irradiation (TBI). Both apoptotic and mitotic Dclk1(+) cells were observed 24 h post-TBI associated with a corresponding loss of intestinal crypts observed at 84 h post-TBI. Although the Notch signaling pathway plays an important role in regulating proliferation and lineage commitment within the intestine, its role in ISC function in response to severe genotoxic injury is not yet fully understood. We employed the microcolony assay to functionally assess the effects of Notch inhibition with difluorophenacetyl-l-alanyl-S-phenylglycine t-butyl ester (DAPT) on intestinal crypt stem cell survival following severe (>8 Gy) radiation injury. Following treatment with DAPT, we observed a nearly 50% reduction in the number of surviving Dclk1(+) crypt epithelial cells at 24 h after TBI and similar reduction in the number of surviving small intestinal crypts at 84 h. These data indicate that inhibition of Notch signaling decreases ISC survival following radiation injury, suggesting that the Notch signaling pathway plays an important role in ISC-mediated crypt regeneration. These results also suggest that crypt epithelial cell Dclk1 expression can be used as one potential marker to evaluate the early survival of ISCs following severe radiation injury.
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