Researchers hope to one day use stem cells to cure burns, patch damaged heart tissue, even grow kidneys and other transplantable organs from scratch. This dream edges nearer to reality every year, but one of the enduring puzzles for come cell researchers is how these remarkable cells understand when it’s time for them to expand in numbers and change into mature, adult cells in order to renew injured or even aging tissue.

The answer for this crucial decision-making process may lie in a most impressive organ: the front tooth of the mouse.

Continuously growing incisors are the defining feature of all rodents, which usually rely on these sharp, chisel-like gnashers for burrowing plus 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 displaying through the gums at the front of the mouth.

Because the front of the tooth gets ground down, a swimming pool of stem cells deep inside the jaw, at the really inner part of the tooth, is constantly building up the back of each incisor and pushing the growing tooth forward — a little like the lead of a mechanical pencil.

“As we grow older our teeth start to wear out, and in character, once you don’t have your teeth anymore, you die. As a result, rodents and many other animals — from elephants to some primates — can grow their teeth continuously, ” said UC San Francisco’s Ophir Klein, MD, PhD, a teacher of orofacial sciences in UCSF’s School of Dental care and of pediatrics in the School of Medicine. “Our lab’s objective is to learn the rules that let mouse incisors grow continuously to help us one day grow teeth within the lab, but also to help us identify general principles which could enable us to understand the processes of tissue revival much more broadly. ”

In a new research, published online April 27, 2017, in Cell Stem Cell , Jimmy Hu, PhD, the postdoctoral researcher in the Klein laboratory, has discovered that indicators from the surrounding tissue are responsible for triggering these dental come cells to leave their normal state of dormancy, hop on the conveyor belt of the growing tooth, and start the process of transforming into mature tooth tissue.

“We usually think of stem cells responding to chemical indicators to start proliferating and differentiating, but here there’s a fantastic interaction between the physical environment and the cells that can fast them to meet the demands of the growing tooth, ” Hu said.

In their study, Hu and co-workers discovered that integrins, proteins that sit in cell walls and link the internal skeleton of cells to the bigger protein scaffolding of the surrounding tissue, trigger a recently described signaling cascade within the stem cells that causes these to begin rapidly multiplying — a process called “proliferation. inch

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

“Our data clearly show that will as stem cells move into their designated proliferating area, they ramp up integrin production. These integrins allow the tissues to interact with extracellular molecules and become triggered to broaden in numbers before eventually producing a large pool associated with mature dental cells, ” Hu said.

Of additional interest to the researchers is the fact that both integrins and YAP — one of the molecules involved in the newly uncovered integrin-triggered signaling cascade — have previously been suggested as a factor in the growth of certain types of tumors, which are considered to share some features of stem cell biology. This getting adds evidence to a growing sense among cancer experts that interactions between cancer cells and the surrounding cells may be a key step in triggering tumor growth.

“Integrins and YAP had been implicated in cancer prior to, but our work connects the two in an organ instead of in a Petri dish, ” Klein said. “Wouldn’t this be nice if the same insights that let us learn to develop new tissues in the lab also lead to improved treatments to prevent the growth of tumors in patients? inch