Keck School professor examines how cells self-organize into complex tissues

By Josh Grossberg

Stem cells have an amazing ability to develop into different kinds of cells of varying shapes and sizes.

How do a group of cells become a thighbone or a kidney or anything else? Without guidance, stem cells will only divide into a mass of more formless cells.

“Organs have to take a shape,” said Cheng-Ming Chuong, professor of pathology at the Keck School of Medicine of USC. “This process is unknown. We are trying to find the principles.”

Chuong and pathology Ph.D. student Ang Li are now a bit closer to finding the answer. The two designed research to see how stem cells form specific shapes—specifically chicken feathers. They uncovered a collection of molecules that trigger the process that turns dome-like primordium into a highly oriented feather filament.

Their findings—a joint effort between the Keck School’s Department of Pathology and the Department of Mathematics at UC Irvine—are published in the April issue of Proceedings of the National Academy of Sciences (PNAS). The research was assisted by grants from the National Institutes of Health and the California Institute of Regenerative Medicine.

Also contributing to the study were Ting-Xin Jiang, Ping Wu and Randall Widelitz, all faculty members in the Keck School’s Department of Pathology.

The process of cells taking shapes—morphogenesis—is at the center of their research. What they discovered is that when feathers begin to form, a network of molecules tells them exactly where to start growing and in what direction to grow.

“Stem cells are equal,” Chuong said. “Some event will determine if they become feather or skin.”

Chicken feathers start as a mere bud of cells. But as the feather begins to grow, that bud begins to take on sharp, defined features. And that nascent plume must grow in a particular way before it turns from an amorphous mass to something recognizable.

“People take it for granted,” Chuong said. “But they should not.”

Li said the trick is learning how the cells do what they do to finally grow into feathers.

“Nature is very smart,” Li said. “Every process involves many molecular regulators. We want to figure out why this happens so robustly. It’s very precise. When the bud is elongated, it needs cells to move in a specific direction.”

Chuong said great strides are being made in the field of regenerative biology, and he sees the day coming when humans can grow new limbs as easily as lizards grow new tails. Getting there will require a lot of work and study, but Chuong is optimistic.

“Are we going to make a bone?” Chuong asked. “That’s the wish. “But to make a symphony, you have to start with a simple tune.”
University of Southern California University of Southern California