Brief Report: Dclk1 Deletion in Tuft Cells Results in Impaired Epithelial Repair After Radiation Injury

Authors

  • Randal May,

    1. Department of Medicine, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
    2. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA
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  • Dongfeng Qu,

    1. Department of Medicine, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
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  • Nathaniel Weygant,

    1. Department of Medicine, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
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  • Parthasarathy Chandrakesan,

    1. Department of Medicine, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
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  • Naushad Ali,

    1. Department of Medicine, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
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  • Stanley A. Lightfoot,

    1. Stowers Institute for Medical Research, Kansas City, Missouri, USA
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  • Linheng Li,

    1. Department of Pathology, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
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  • Sripathi M. Sureban,

    1. Department of Medicine, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
    2. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA
    3. Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
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  • Courtney W. Houchen

    Corresponding author
    1. Department of Medicine, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
    2. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA
    3. Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
    • Correspondence: Courtney W. Houchen, M.D., Department of Medicine, The University of Oklahoma Health Sciences Center, 920 Stanton L. Young Blvd, WP 1360, Oklahoma City, Oklahoma 73104, USA. Telephone: 405-271-5428; Fax: 405-271-5450; e-mail: courtney-houchen@ouhsc.edu

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Abstract

The role of Dclk1+ tuft cells in the replacement of intestinal epithelia and reestablishing the epithelial barrier after severe genotoxic insult is completely unknown. Successful restoration requires precise coordination between the cells within each crypt subunit. While the mechanisms that control this response remain largely uncertain, the radiation model remains an exceptional surrogate for stem cell-associated crypt loss. Following the creation of Dclk1-intestinal-epithelial-deficient Villin-Cre;Dclk1flox/flox mice, widespread gene expression changes were detected in isolated intestinal epithelia during homeostasis. While the number of surviving crypts was unaffected, Villin-Cre;Dclk1flox/flox mice failed to maintain tight junctions and died at approximately 5 days, where Dclk1flox/flox mice lived until day 10 following radiation injury. These findings suggest that Dclk1 plays a functional role critical in the epithelial restorative response. Stem Cells 2014;32:822–827

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