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Mouse teeth provide insights into tissue regeneration, cancer research.

SAN FRANCISCO Calif., April 27, 2017 -- How do stem cells know when it's to expand in numbers and transform into mature, adult cells to renew injured or aging tissue?

The answer to this crucial decision-making process may be found in a most remarkable tissue: the front tooth of the mouse.

Constantly growing incisors are the defining feature of all rodents, which rely on these sharp, chisel-like gnashers for burrowing and self-defense as well as gnawing food.

Inside the jaw, a mouse's incisors look more like a walrus's tusks or the teeth of a saber-toothed tiger, with only the sharpened tips showing through the gums at the front of the mouth.

As the front of the tooth gets ground down, a pool of stem cells deep inside the jaw, at the very inner part of the tooth, is constantly building up the back of each incisor and pushing the growing tooth forward.

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"As we grow older our teeth start to wear out, and in nature, once you don't have your teeth anymore, you die. As a result, mice and many other animals--from elephants to some primates--can grow their teeth continuously," said Ophir Klein, of the UCSF School of Dentistry. "Our lab's objective is to learn the rules that let mouse incisors grow continuously to help us one day grow teeth in the lab, but also to help us identify general principles that could enable us to understand the processes of tissue renewal much more broadly."

In a new study, researchers discovered that signals from the surrounding tissue are responsible for triggering these dental stem cells to leave their normal state of dormancy and begin transforming into mature tooth tissue.

In other words, there's an interaction between the physical environment and the cells that can prompt them to meet the demands of the growing tooth.

The researchers discovered that integrins, which are proteins that sit in cell membranes and link the internal skeleton of cells to the larger protein scaffolding of the surrounding tissue, trigger a newly described signaling cascade within the stem cells that causes them to begin rapidly proliferating.

It's not clear yet exactly what external signals are responsible for triggering the stem cells to proliferate, the authors say, but they propose that the cells could be detecting that they have moved into a region where the back of the tooth needs to actively produce more cells based on changes in local tissue stiffness or the physical forces pulling and pushing on the cells.

The data clearly show that as stem cells move into their designated proliferating space, they ramp up integrin production. Integrins allow the cells to interact with extracellular molecules and become triggered to expand in numbers before eventually producing a large pool of mature dental cells.

Citation: Jimmy Kuang-Hsien Hu et al., "An FAKYAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice," Cell Stem Cell, 2017; DOI: 10.1016/j.stem.2017.03.023

Abstract/Article: http://bit.ly/2pUuLv1

Contact: Ophir D. Klein, ophir.klein@ucsf.edu

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Title Annotation:Basic Research
Publication:Stem Cell Research News
Date:May 8, 2017
Words:504
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