Tuft cells

Sato, Atsuko

doi:10.1111/j.1447-073x.2007.00188.x

Cited by 77 publications

(80 citation statements)

References 76 publications

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“…However, previous reports have suggested that tuft cells are often found in close proximity to neurons (14,18,39), and our collaborators have demonstrated that functional innervation regulates epithelial homeostasis and response to injury (52). Indeed, we found that DCLK1 + cells were sustained when organoids were cocultured with neurons and therefore represent, to the best of our knowledge, the first cell type that cannot be generated in organoid cultures in the absence of nonepithelial niche signals.…”

Section: Discussionmentioning

confidence: 58%

“…These results suggested that nonepithelial signals might be critical for tuft cell maintenance and longevity in organoid cultures. Given that previous reports suggested an association between epithelial tuft cells and neuronal structures (14,18,39), we hypothesized that neuronal input might support tuft cell survival in colonic, intestinal, and gastric organoid cultures. To test this hypothesis, we established a coculture system of primary neurons isolated from the spinal cord (40) To test whether functional innervation was associated with tuft cell survival in vivo, we examined paired biopsies from intestinal transplant patients (n = 2) and found that while the transplanted graft (which was extrinsically denervated) lacked DCLK1 + cells, the endogenous intestine (which was normally innervated) had a normal complement of DCLK1 + cells (Supplemental Figure .…”

Section: Dclk1 + Cells In In Vitromentioning

confidence: 99%

“…More recently, a fifth epithelial cell type, known as the tuft cell, has been recognized and shown to be LGR5 derived (11). This rare cell type, originally described in the rodent trachea (12) and stomach (13) more than 60 years ago, was subsequently found throughout the entire digestive and respiratory tracts (14). Tuft cells have been implicated in chemoreception (14)(15)(16)(17)(18) and express proteins of the eicosanoid pathway such as cyclo-oxygenase-1 and cyclo-oxygenase-2 (19).…”

Section: Introductionmentioning

confidence: 99%

“…This rare cell type, originally described in the rodent trachea (12) and stomach (13) more than 60 years ago, was subsequently found throughout the entire digestive and respiratory tracts (14). Tuft cells have been implicated in chemoreception (14)(15)(16)(17)(18) and express proteins of the eicosanoid pathway such as cyclo-oxygenase-1 and cyclo-oxygenase-2 (19). Recently, tuft cells have been shown to express the protein doublecortinlike kinase 1 protein (DCLK1, previously referred to as KIAA0369 or DCAMKL1), which encodes a microtubule-associated protein with a C-terminal serine-threonine kinase domain (20,21).…”

Section: Introductionmentioning

confidence: 99%

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Long-lived intestinal tuft cells serve as colon cancer–initiating cells

et al. 2014

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Section: Discussionmentioning

confidence: 58%

Section: Dclk1 + Cells In In Vitromentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Long-lived intestinal tuft cells serve as colon cancer–initiating cells

et al. 2014

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“…Goblet cells secrete mucins and thereby establish and maintain the protective mucus layer (Kim and Ho, 2010). Tuft cells comprise a rare cell population marked by doublecortin-like kinase 1 (Dclk1) expression (Gerbe et al, 2011) and are implicated in chemoreception (Gerbe et al, 2012;Sato, 2007). Enteroendocrine cells are the hormone-producing cells in the intestine.…”

Section: Introductionmentioning

confidence: 99%

Lmx1a functions in intestinal serotonin-producing enterochromaffin cells downstream of Nkx2.2

et al. 2016

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Intestinal hormone-producing cells represent the largest endocrine system in the body, but remarkably little is known about enteroendocrine cell type specification in the embryo and adult. We analyzed stage-and cell type-specific deletions of Nkx2.2 and its functional domains in order to characterize its role in the development and maintenance of enteroendocrine cell lineages in the mouse duodenum and colon. Although Nkx2.2 regulates enteroendocrine cell specification in the duodenum at all stages examined, it controls the differentiation of progressively fewer enteroendocrine cell populations when deleted from Ngn3 + progenitor cells or in the adult duodenum. During embryonic development Nkx2.2 regulates all enteroendocrine cell types, except gastrin and preproglucagon. In developing Ngn3+ enteroendocrine progenitor cells, Nkx2.2 is not required for the specification of neuropeptide Y and vasoactive intestinal polypeptide, indicating that a subset of these cell populations derive from an Nkx2.2-independent lineage. In adult duodenum, Nkx2.2 becomes dispensable for cholecystokinin and secretin production. In all stages and Nkx2.2 mutant conditions, serotonin-producing enterochromaffin cells were the most severely reduced enteroendocrine lineage in the duodenum and colon. We determined that the transcription factor Lmx1a is expressed in enterochromaffin cells and functions downstream of Nkx2.2. Lmx1a-deficient mice have reduced expression of Tph1, the rate-limiting enzyme for serotonin biosynthesis. These data clarify the function of Nkx2.2 in the specification and homeostatic maintenance of enteroendocrine populations, and identify Lmx1a as a novel enterochromaffin cell marker that is also essential for the production of the serotonin biosynthetic enzyme Tph1.

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Peroral Toxicity

Brock¹

2009

General, Applied and Systems Toxicology

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Numerous factors will affect the passage of drugs and chemicals through the gastrointestinal tract and into systemic circulation. These factors involve anatomical and physiological features, species differences and biochemical features, including intestinal metabolism and effects on transporters. With regard to assessing potential risk of humans to chemicals, these features will need to be considered as there will be differences between experimental animals and humans. The cellular environment of the gastrointestinal tract and the molecular mechanisms of absorption will have a major influence on the bioavailability of drugs and chemicals. The pH of the local cell environment will affect the ionization status of the compound, whereas a drug may inhibit cellular transport of other substances, for example, nutrients, potentially having an affect on the nutritional status of the animal. Moreover, there has been demonstrated evidence that some xenobiotics will affect the metabolic status of the gastrointestinal tract. Cytochrome P450 3A is the more common form of cytochrome isoforms found in the intestine, but there are numerous examples that can inhibit, or induce, metabolism much in the same way that hepatic metabolism is affected by chemicals. In addition, the bacterial content of the gastrointestinal tract can affect the absorption of substances primarily by bacterial metabolism. The fasting status of the animal also will affect absorption, and is probably one the more important considerations in the design of a toxicology study. It has been clearly shown that absorption occurs more readily in the fasted animal, and that toxicity may be enhanced since there is a greater surface area of the gastrointestinal tract available for absorption. Finally, chemical interactions will potentially modify absorption through binding of the compound or changing the local cellular environment. From a practical perspective, oral administration of compounds is the most common method for compound administration in toxicology studies. In oral toxicity studies, one will need to consider the drug formulation and the potential effects of the vehicle on the stability as well as the potential toxicity of the vehicle. For the most part, a majority of the vehicles being used currently in laboratories have a long history of use such that toxicity of the vehicle does not become too much of a concern, but the principle of toxicology, the dose makes the poison, should always be a consideration.

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Tuft cells

Cited by 77 publications

References 76 publications

Long-lived intestinal tuft cells serve as colon cancer–initiating cells

Long-lived intestinal tuft cells serve as colon cancer–initiating cells

Lmx1a functions in intestinal serotonin-producing enterochromaffin cells downstream of Nkx2.2

Peroral Toxicity

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