Stem cells use signal orientation to guide division, Stanford study shows

Public release date: 21-Mar-2013 [ | E-mail | Share ]

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. Cells in the body need to be acutely aware of their surroundings. A signal from one direction may cause a cell to react in a very different way than if it had come from another direction. Unfortunately for researchers, such vital directional cues are lost when cells are removed from their natural environment to grow in an artificial broth of nutrients and growth factors.

Now, researchers at the Stanford University School of Medicine and the Howard Hughes Medical Institute have devised a way to mimic in the laboratory the spatially oriented signaling that cells normally experience.

Using the technique, they've found that the location of a "divide now" signal on the membrane of a human embryonic stem cell governs where in that cell the plane of division occurs. It also determines which of two daughter cells remains a stem cell and which will become a progenitor cell to replace or repair damaged tissue.

The research offers an unprecedented, real-time glimpse into the intimate world of a single stem cell as it decides when and how to divide, and what its daughter cells should become. But the implications stretch beyond stem cells.

"In the body, it is likely that every cell grows and differentiates in some kind of orientation," said Roeland Nusse, PhD, professor of developmental biology. "Without this guidance, specialized cells would end up in the wrong place. Now, we can study the division of single mammalian cells in real time and see them dividing and differentiating in an oriented way."

Understanding this process of self-renewal and specialization (or differentiation) is critical to learning how to truly harness the power of stem cells for future therapies. But polarity, or the ability of a cell to distinguish its top from bottom or left from right, is also vital to many other biological processes. For example, hair grows out of, rather than into, the body, and tissues develop with orderly layers of specific cell types.

Nusse is the senior author of the work, which will be published March 23 in Science. He is also a member of the Stanford Cancer Institute, the Stanford Institute for Stem Cell Biology and Regenerative Medicine and HHMI investigator. Shukry Habib, PhD, a research associate and Siebel Scholar, is the lead author of the work. The study was funded in part by a grant from the California Institute of Regenerative Medicine.

Stem cells are unique in their ability to both self-renew and to generate progenitor cells that can become many cell types. A single stem cell can divide to make two new stem cells or, in a process called asymmetric division, give rise to one stem cell and one progenitor cell. Because the original parent cell is replaced by the two new daughter cells, this approach ensures that stem cells will not be depleted during periods of development or healing.

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Stem cells use signal orientation to guide division, Stanford study shows