Cellular Shape-Shifters: Scientists Uncover Variation in Human Cell Organization

The Allen Institute for Cell Science has made a significant scientific discovery, according to a paper published in the journal Nature. The team at the institute has developed a method for quantifying the internal organization of human cells, a concept that has previously proven difficult to measure. By working with hundreds of thousands of high-resolution images, the scientists were able to capture details about the variation in cell shape among genetically identical cells grown under identical conditions.

The study was led by Susanne Rafelski, Ph.D., Deputy Director of the Allen Institute for Cell Science, and Senior Scientist Matheus Viana, Ph.D. According to Rafelski, the way in which cells are organized can provide insight into their behavior and identity. The new method offers a roadmap for biologists to understand the organization of different kinds of cells in a measurable, quantitative way, as well as reveals key organizational principles of the human induced pluripotent stem cells studied by the team.

Understanding how cells organize themselves under healthy conditions, and the full range of variability contained within "normal," can help scientists better understand what goes wrong in disease. The image dataset, genetically engineered stem cells, and code that went into this study are all publicly available for other scientists to use.

To develop the new method, the Allen Institute team first built a collection of stem cells that were genetically engineered to light up different internal structures under a fluorescent microscope. They then captured high-resolution, 3D images of more than 200,000 cells, each with 25 labeled structures. The scientists wanted to know how these tiny cellular structures arranged themselves concerning each other and if there was any consistency in their placement.

However, the team encountered a challenge when comparing the same structure between two different cells. Even though the cells were genetically identical and grown in the same laboratory environment, their shapes varied substantially. This made it impossible to compare the position of a particular structure in two different cells if one was short and blobby and the other was long and pear-shaped. To overcome this issue, the team developed a "shape space" that objectively describes the shape of each cell. This allowed them to compare the position of a structure in cells with different shapes.

The scientists found that certain structures in the cells tended to be located in specific areas, while others were more randomly distributed. This finding could have important implications for understanding the organization and function of cells, as well as for studying how cells change in health and disease.