Scientific Earth Conscientious

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Scientists at the Monell Center have identified the location and certain genetic characteristics of taste stem cells on the tongue. Identification of progenitors may someday help treat clinical taste dysfunction

Posted by Scientific Earth Conscientious on February 4, 2013

Scanning electron microscopy image illustrates the dorsal view of an E15.5 embryonic tongue and papilla types. Black arrowheads point to fungiform papillae on the anterior oral tongue; black arrow points to the single circumvallate papilla in the back. White arrowhead at the tip points to the median furrow. The straight line marks the orientation for sectioning in the sagittal plane. B: H and E stained sagittal section of an E15.5 tongue to illustrate the orientation for all images of tongue sections. Black arrowheads point to fungiform papillae. Scale bars: 250 μm.

Scanning electron microscopy image illustrates the dorsal view of an E15.5 embryonic tongue and papilla types. Black arrowheads point to fungiform papillae on the anterior oral tongue; black arrow points to the single circumvallate papilla in the back. White arrowhead at the tip points to the median furrow. The straight line marks the orientation for sectioning in the sagittal plane. B: H and E stained sagittal section of an E15.5 tongue to illustrate the orientation for all images of tongue sections. Black arrowheads point to fungiform papillae. Scale bars: 250 μm.

Scientists at the Monell Center have identified the location and certain genetic characteristics of taste stem cells on the tongue. The findings will facilitate techniques to grow and manipulate new functional taste cells for both clinical and research purposes.

“Cancer patients who have taste loss following radiation to the head and neck and elderly individuals with diminished taste function are just two populations who could benefit from the ability to activate adult taste stem cells,” said Robert Margolskee, M.D., Ph.D., a molecular neurobiologist at Monell who is one of the study’s authors.

Taste cells are located in clusters called taste buds, which in turn are found in papillae, the raised bumps visible on the tongue’s surface.

Two types of taste cells contain chemical receptors that initiate perception of sweet, bitter, umami, salty, and sour taste qualities. A third type appears to serve as a supporting cell.

A remarkable characteristic of these sensory cells is that they regularly regenerate. All three taste cell types undergo frequent turnover, with an average lifespan of 10-16 days. As such, new taste cells must constantly be regenerated to replace cells that have died.

For decades, taste scientists have attempted to identify the stem or progenitor cells that spawn the different taste receptor cells. The elusive challenge also sought to establish whether one or several progenitors are involved and where they are located, whether in or near the taste bud.

Drawing on the strong physiological relationship between oral taste cells and endocrine (hormone producing) cells in the intestine, the Monell team used a marker for intestinal stem cells to probe for stem cells in taste tissue on the tongue.

Stains for the stem cell marker, known as Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5), showed two patterns of expression in taste tissue. The first was a strong signal underlying taste papillae at the back of the tongue and the second was a weaker signal immediately underneath taste buds in those papillae.

The Monell scientists hypothesize that the two levels of expression could indicate two different populations of cells. The cells that more strongly express Lgr5 could be true taste stem cells, whereas those with weaker expression could represent those stem cells that have begun the transformation into functional taste cells.

Additional studies revealed that the Lgr5-expressing cells were capable of becoming any one of the three major taste cell types.

The findings are published online in the journal Stem Cells.

“This is just the tip of the iceberg,” said senior author Peihua Jiang, Ph.D., also a Monell molecular neurobiologist. “Identification of these cells opens up a whole new area for studying taste cell renewal, and contributes to stem cell biology in general.”

Future studies will focus on identifying the factors that program the Lgr5-expressing cells to differentiate into the different taste cell types, and explore how to grow these cells in culture, thus providing a renewable source of taste receptor cells for research and perhaps even clinical use.

 

 

Other authors from Monell that contributed to the work are Karen Yee, Yan Li and Kevin Redding.

Research reported in this publication was supported by the National Institute on Deafness and Other Communication Disorders under award numbers DC0101842, DC003055, and 1P30DC011735, and National Institute of Diabetes and Digestive and Kidney Diseases grant DK081421. Both institutes are part of the National Institutes of Health. Additional funding was provided by the Commonwealth of Pennsylvania Department of Health.

The Monell Chemical Senses Center is an independent nonprofit basic research institute based in Philadelphia, Pennsylvania. For 45 years, Monell has advanced scientific understanding of the mechanisms and functions of taste and smell to benefit human health and well-being. Using an interdisciplinary approach, scientists collaborate in the programmatic areas of sensation and perception; neuroscience and molecular biology; environmental and occupational health; nutrition and appetite; health and well-being; development, aging and regeneration; and chemical ecology and communication. For more information about Monell, visit www.monell.org.

 

Contact: Leslie Stein
stein@monell.org
267-519-4707
Monell Chemical Senses Center

 

Diagram to illustrate distribution of NC cells and NC-derived cells in developing tongue. A: Cross section of an early stage embryo at a cranial level. The delaminated, migratory NC cells (blue) are located at both sides lateral to neural tube (red), under the ectodermal sheet (pink). B: Sagittal section of branchial arch I (tongue primordium) before tongue emerges. The anterior tip is toward to the right and dorsal surface up (also applies to C and D). Migrated NC cells (blue) are scattered in the epithelium and broadly distributed in the mesenchyme. C: Sagittal section of anterior region of oral tongue with developing fungiform papillae on the dorsal surface. NC derived cells (blue) are clustered in tongue epithelium within and between papillae. In tongue mesenchyme, NC derived cells are more restricted under the epithelium. D: A fungiform papilla with single taste bud at the apex. NC derived cells are within taste buds and in the surrounding papilla epithelium. Also, NC derived cells are densely distributed in the mesenchymal core of papillae. We propose that NC cells (A, blue cells) migrate into the epithelium and mesenchyme of tongue primordium (B) at early embryonic stage. The NC cells in tongue epithelium acquire epithelial phenotype and undergo cell proliferation and differentiation to become clusters within and between papillae (C). A population of NC-derived cells is within early taste buds (D). In tongue mesenchyme, NC-derived cells are progressively restricted to connective tissues under tongue epithelium and densely distributed in the mesenchymal core of taste papillae (C, D).

Diagram to illustrate distribution of NC cells and NC-derived cells in developing tongue. A: Cross section of an early stage embryo at a cranial level. The delaminated, migratory NC cells (blue) are located at both sides lateral to neural tube (red), under the ectodermal sheet (pink). B: Sagittal section of branchial arch I (tongue primordium) before tongue emerges. The anterior tip is toward to the right and dorsal surface up (also applies to C and D). Migrated NC cells (blue) are scattered in the epithelium and broadly distributed in the mesenchyme. C: Sagittal section of anterior region of oral tongue with developing fungiform papillae on the dorsal surface. NC derived cells (blue) are clustered in tongue epithelium within and between papillae. In tongue mesenchyme, NC derived cells are more restricted under the epithelium. D: A fungiform papilla with single taste bud at the apex. NC derived cells are within taste buds and in the surrounding papilla epithelium. Also, NC derived cells are densely distributed in the mesenchymal core of papillae. We propose that NC cells (A, blue cells) migrate into the epithelium and mesenchyme of tongue primordium (B) at early embryonic stage. The NC cells in tongue epithelium acquire epithelial phenotype and undergo cell proliferation and differentiation to become clusters within and between papillae (C). A population of NC-derived cells is within early taste buds (D). In tongue mesenchyme, NC-derived cells are progressively restricted to connective tissues under tongue epithelium and densely distributed in the mesenchymal core of taste papillae (C, D).

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