Inner Workings: Microscopy lights up stem cells in action [Cell Biology]

As developmental and cell biologist Valentina Greco stood on a stage in Philadelphia last December, candid time-lapse shots of some of the body’s most elusive cells flashed behind her in quick succession. These stem cells, photographed in a living mouse , were caught in the acts of dividing, differentiating, and interacting with neighbors. Such videos are more than just captivating cellular cinema—they could reveal key details about how stem cells work. Stem cell biologists are developing microscopy techniques to track individual cells in living animals for weeks or even months at a time. Here, the cells in a mouse’s hair follicles glow under a scope operated by Valentina Greco’s team at Yale University. Image courtesy of Panteleimon Rompolas (University of Pennsylvania, Philadelphia). Cell biology is in the midst of a microscopy boom, and stem cell researchers in particular are coming up with inventive techniques for capturing live images of these enigmatic cells in their native habitats. Scattered throughout adult tissue, stem cells help maintain tissue function, heal wounds, and in the case of animals such as the zebrafish and axolotl, regenerate entire limbs. Greco, a professor at Yale University, is among the pioneers of using novel combinations of microscopes, fluorescent markers, and sample preparations that light up cellular interactions inside living model organisms to reveal the cues and triggers that prompt these versatile cells to action. As a microscopist, Greco felt compelled to study the dynamics of stem cell regeneration by watching cells in a living animal. “I followed what I know,” she says. “It was easier for me to walk that path than not to.” That’s not to say it’s been easy. She and her team had to focus a high-power microscope on a perfectly still mouse whose cells expressed the right combination of fluorescent markers. Today, Greco can …