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Gastric tuft cells express DCLK1 and are expanded in hyperplasia

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Abstract

Epithelial tuft cells are named after their characteristic microtubule bundles located at the cell apex where these are exposed to the luminal environment. As such, tuft cells are found in multiple organs, including the gastrointestinal (GI) tract where the apical “tuft” is hypothesized to detect and transmit environmental signals. Thus, the goal of our study was to characterize gastric tuft cells during GI tract development, then subsequently in the normal and metaplastic adult stomach. GI tracts from mouse embryos, and newborn and postnatal mice were analyzed. Tuft cells were identified by immunohistochemistry using acetylated-α-tubulin (acTub) antibody to detect the microtubule bundle. Additional tuft cell markers, e.g., doublecortin-like kinase 1 (DCLK1), were used to co-localize with acTub. Tuft cells were quantified in human gastric tissue arrays and in mouse stomachs with or without inflammation. In the developing intestine, tuft cells in both the crypts and villi expressed all markers by E18.5. In the stomach, acTub co-localized with DCLK1 and other established tuft cell markers by E18.5 in the antrum, but not until postnatal day 7 in the corpus, with the highest density of tuft cells clustered at the forestomach ridge. Tuft cell numbers increased in hyperplastic human and mouse stomachs. In the adult GI tract, the tuft cell marker acTub co-expressed with DCKL1 and chemosensory markers, e.g.,TRPM5. In summary, tuft cells appear in the gastric antrum and intestine at E18.5, but their maximal numbers in the corpus are not achieved until after weaning. Tuft cell numbers increase with inflammation, hyperplasia, and metaplasia.

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Acknowledgments

This study was supported by NIH Grant P01-DK62041 (J.L.M.), NIH Grants RO1-DK078926 (L.C.S.), and University of Michigan Digestive Disease Center Grant P30-DK-34933.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Pl. BSRBI, Rm.2051, Ann Arbor, MI, 48109-2200, USA

    Milena Saqui-Salces, Mohamad El-Zaatari, Linda C. Samuelson & Juanita L. Merchant

  2. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA

    Theresa M. Keeley, Linda C. Samuelson & Juanita L. Merchant

  3. Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA

    Ann S. Grosse, Xiaotan T. Qiao & Deborah L. Gumucio

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  1. Milena Saqui-Salces
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  2. Theresa M. Keeley
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  3. Ann S. Grosse
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  4. Xiaotan T. Qiao
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  5. Mohamad El-Zaatari
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  7. Linda C. Samuelson
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Correspondence to Juanita L. Merchant.

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Supplementary Figure 1 (JPG 373 kb)

Supplementary Figure 2

: Co-localization of acTub (red) with known tuft cells markers: (A) guanine nucleotide binding protein α-transducing 3 (GNAT3, also called α-gustducin, green) and (B) Villin-1 (green) shown in an isolated gland prep from the squamous/columnar epithelium border region. The basal membranes are indicated with white dashed lines in panel A. C) Glucagon-like peptide 1 (GLP-1) (green) also co-localized with acTub (red) in tuft cells. (TIFF 4462 kb)

Supplementary Figure 3 (JPG 373 kb)

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Supplementary material 7 (DOC 27 kb)

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Saqui-Salces, M., Keeley, T.M., Grosse, A.S. et al. Gastric tuft cells express DCLK1 and are expanded in hyperplasia. Histochem Cell Biol 136, 191–204 (2011). https://doi.org/10.1007/s00418-011-0831-1

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