Allen Institute for Cell Science researchers have developed a new technique that will enable better understanding of human heart muscle cells. The method, described in a study published April 4 in the journal Stem Cell Reports, lays the groundwork for possible future studies of genetic cardiac defects and provides a key marker that could benefit cardiac regenerative medicine research.
The method, known as “silent gene editing,” allows researchers to label genes that are silent, or switched off, in human induced pluripotent stem cells, or hiPS cells, but active in differentiated cells derived from them. This strategy addresses a challenge in the stem cell field, namely, labeling something that’s unseen. To accomplish this silent gene editing, the researchers couple a fluorescent tag specific to the silent gene with a second fluorescent label that will light up in the undifferentiated hiPS cells, allowing them to identify cells in which the gene editing has worked. Once identified, that second fluorescent tag is removed, leaving the label specific to the silent gene.
The researchers used the method to add fluorescent tags to genes that are silent in hiPS cells but switched on during differentiation into heart muscle cells, or cardiomyocytes, labeling five different pieces of one cardiomyocyte structure. That structure, known as a sarcomere, enables muscle cells to contract and relax, the key attribute of cardiomyocytes that allows our hearts to beat in rhythm.