Picking faces out of a crowd: genetic labels for identification of proteins in correlated light and electron microscopy imaging.

Correlated light and electron microscopic (CLEM) imaging is a powerful method for dissecting cell and tissue function at high resolution. Each imaging mode provides unique information, and the combination of the two can contribute to a better understanding of the spatiotemporal patterns of protein expression, trafficking, and function. Critical to these methods is the use of genetically appended tags that highlight specific proteins of interest in order to be able to pick them out of their complex cellular environment. Here we review and discuss the current generation of genetic labels for direct protein identification by CLEM, addressing their relative strengths and weaknesses and in what experiments they would be most useful.