The power of gene editing

June 29, 2016

Visualizing the complexity of cells and all their machinery is not easy. A cell may express thousands of proteins that cluster around scores of organelles, and identifying where each organelle sits in space at any given moment is often a cloudy proposition. Many labs use transfection techniques or other expression methods, which can flood a cell with a particular tagged protein so many non-specific areas of the cell light up under the microscope. While useful in many ways, these techniques lack the specificity needed to image more accurately, and ultimately generate the kind of predictive models of cellular behavior we seek to create and share.

The Allen Institute for Cell Science is taking a different approach to labeling cells for imaging studies. Starting with human induced pluripotent stem (hiPS) cells, we are using gene editing methods to alter the genomes of these diploid cells to produce fluorescent proteins, each outlining just one organelle. The first images coming back from these assays show just how powerful gene editing techniques can be to illuminate precise structures in highly complex cells.

The video above features several organelles we've just begun to image. They include:

  • Desmosomes, which form cell to cell junctions and are particularly prominent in epithelia, cardiac muscle and other cell types.

  • Mitochondria, which generate most of the cell's energy.

  • Microtubules, which are a major component of the cell’s internal skeleton (cytoskeleton) and separate chromosomes during cell division (see the “mitotic spindles” in the three cells in the video).

The technique is time and labor intensive to be sure, but these early results justify the choice. As we develop more hiPS cell lines and generate more images at scale, the power of gene editing will shine through even more clearly.