Stem cells in the laboratory lead a seemingly idyllic life, spending most of their time being gently sloshed around in a warm bath of yummy nutrients. But this pampered, directionless lifestyle presents a problem for scientists trying to understand how the cells organize themselves in the body. In “real life” it matters quite a lot who your neighbors are and from what direction the various messages and signals that guide cellular life originate. Until now, however, it’s been nearly impossible for scientists to study how such localized signals affect stem cells.
Now developmental biologist Roeland Nusse, PhD, and Shukry Habib, PhD, a research associate and Siebel Scholar, have devised an ingenious way to mimic localized signals by binding a signaling molecule (in this case, a protein called Wnt3a) to an inert microscopic bead. They then traced the actions of individual mouse embryonic stem cells bound to only one bead–meaning the cell was receiving the Wnt3a signal from only one location on its membrane. The research was published yesterday in Science (subscription required). From our release:
The effect of the localized signal was clear. In 75 percent of cases, the stem cell began to divide in a very specific orientation, with the plane of division occurring perpendicularly to the location of the incoming signal. In contrast, only 12 percent of cells exposed to beads bound to a control protein exhibited similar patterns of division.
Habib and his colleagues also found that the daughter cell closest to the Wnt3a signal expressed proteins showing it was maintaining its pluripotency, or ability to function as a stem cell like its parent. The one farthest from the signal, however, expressed proteins indicating that it was beginning to differentiate.
The new technique should help researchers further their understanding of what’s called asymmetric division. That’s when a parent stem cell divides into two cells: one a stem cell like itself, and the other a more-differentiated cell that can repair or replace damaged tissue. This ability ensures that stem cells are not depleted.
Lessons learned from this technique are likely to extend beyond stem cell science. As Nusse explains:
In the body, it is likely that every cell grows and differentiates in some kind of orientation. 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.