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Local microenvironment provides important cues for cell differentiation in lingual epithelia.

ABSTRACT: Transgenic Keratin14-rtTA-PTR mice specifically express Keratin14 (K14) in the tongue epithelia, as well as co-express EGFP and the dominant negative ΔTgfbr2 genes upon treatment with Doxycycline (Dox). As TGF-β signaling negatively regulates the stem cell cycle and proliferation, its disruption by Dox induction in these transgenic mice shortens the cell cycle and allows observation of the final fate of those mutated cell lineages within a short period of time. Here, we used inducible transgenic mice to track the K14+ cells through the cell migration stream by immunohistochemical an immunofluorescent imaging. We showed that these cells have different development patterns from the tip to posterior of the tongue, achieved presumably by integrating positional information from the microenvironment. The expression of the K14 gene was variable, depending on the location of the tongue and papillae. Disruption of TGF-β signaling in K14+ progenitor cells resulted in proliferation of stem cell pools.

SUBMITTER: Li F

PROVIDER: S-EPMC3325925 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Local microenvironment provides important cues for cell differentiation in lingual epithelia.

Li Feng F Zhou Mingliang M

PloS one 20120413 4

Transgenic Keratin14-rtTA-PTR mice specifically express Keratin14 (K14) in the tongue epithelia, as well as co-express EGFP and the dominant negative ΔTgfbr2 genes upon treatment with Doxycycline (Dox). As TGF-β signaling negatively regulates the stem cell cycle and proliferation, its disruption by Dox induction in these transgenic mice shortens the cell cycle and allows observation of the final fate of those mutated cell lineages within a short period of time. Here, we used inducible transgenic ...[more]

PMID: 22514735

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Project description:Peptide hormones and their cognate receptors belonging to neuropeptide Y (NPY) family mediate diverse biological functions in a number of tissues. Recently, we discovered the presence of the gut satiation peptide YY (PYY) in saliva of mice and humans and defined its role in the regulation of food intake and body weight maintenance. Here we report the systematic analysis of expression patterns of all NPY receptors (Rs), Y1R, Y2R, Y4R, and Y5R in lingual epithelia in mice. Using four independent assays, immunohistochemistry, in situ hybridization, immunocytochemistry and RT PCR, we show that the morphologically different layers of the keratinized stratified epithelium of the dorsal layer of the tongue express Y receptors in a very distinctive yet overlapping pattern. In particular, the monolayer of basal progenitor cells expresses both Y1 and Y2 receptors. Y1Rs are present in the parabasal prickle cell layer and the granular layer, while differentiated keratinocytes display abundant Y5Rs. Y4Rs are expressed substantially in the neuronal fibers innervating the lamina propria and mechanoreceptors. Basal epithelial cells positive for Y2Rs respond robustly to PYY(3-36) by increasing intracellular Ca(2+) suggesting their possible functional interaction with salivary PYY. In taste buds of the circumvallate papillae, some taste receptor cells (TRCs) express YRs localized primarily at the apical domain, indicative of their potential role in taste perception. Some of the YR-positive TRCs are co-localized with neuronal cell adhesion molecule (NCAM), suggesting that these TRCs may have synaptic contacts with nerve terminals. In summary, we show that all YRs are abundantly expressed in multiple lingual cell types, including epithelial progenitors, keratinocytes, neuronal dendrites and TRCs. These results suggest that these receptors may be involved in the mediation of a wide variety of functions, including proliferation, differentiation, motility, taste perception and satiation.

Project description:It is well established that collagen alignment in the breast tumor microenvironment provides biophysical cues to drive disease progression. Numerous mechanistic studies have demonstrated that tumor cell behavior is driven by the architecture and stiffness of the collagen matrix. However, the mechanical properties within a 3D collagen microenvironment, particularly at the scale of the cell, remain poorly defined. To investigate cell-scale mechanical cues with respect to local collagen architecture, we employed a combination of intravital imaging of the mammary tumor microenvironment and a 3D collagen gel system with both acellular pNIPAAm microspheres and MDA-MB-231 breast carcinoma cells. Within the in vivo tumor microenvironment, the displacement of collagen fiber was identified in response to tumor cells migrating through the stromal matrix. To further investigate cell-scale stiffness in aligned fiber architectures and the propagation of cell-induced fiber deformations, precise control of collagen architecture was coupled with innovative methodology to measure mechanical properties of the collagen fiber network. This method revealed up to a 35-fold difference in directional cell-scale stiffness resulting from contraction against aligned fibers. Furthermore, the local anisotropy of the matrix dramatically altered the rate at which contractility-induced fiber displacements decayed over distance. Together, our results reveal mechanical properties in aligned matrices that provide dramatically different cues to the cell in perpendicular directions. These findings are supported by the mechanosensing behavior of tumor cells and have important implications for cell-cell communication within the tissue microenvironment. STATEMENT OF SIGNIFICANCE: It is widely appreciated that the architecture of the extracellular matrix impacts cellular behavior in normal and disease states. Numerous studies have determined the fundamental role of collagen matrix architecture on cellular mechanosensing, but effectively quantifying anisotropic mechanical properties of the collagen matrix at the cell-scale remains challenging. Here, we developed innovative methodology to discover that collagen alignment results in a 35-fold difference in cell-scale stiffness and alters contractile force transmission through the fiber network. Furthermore, we identified bias in cell response along the axis of alignment, where local stiffness is highest. Overall, our results define cell-scale stiffness and fiber deformations due to collagen architecture that may instruct cell communication within a broad range of tissue microenvironments.

Dataset Information

Local microenvironment provides important cues for cell differentiation in lingual epithelia.

Publications

Local microenvironment provides important cues for cell differentiation in lingual epithelia.

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