Genetically encoded barcodes for correlative volume electron microscopy

Felix Sigmund, Oleksandr Berezin, Sofia Beliakova, Bernhard Magerl, Martin Drawitsch, Alberto Piovesan, Filipa Gonçalves, Silviu Vasile Bodea, Stefanie Winkler, Zoe Bousraou, Martin Grosshauser, Eleni Samara, Jesús Pujol-Martí, Sebastian Schädler, Chun So, Stephan Irsen, Axel Walch, Florian Kofler, Marie Piraud, Joergen KornfeldKevin Briggman, Gil Gregor Westmeyer

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

While genetically encoded reporters are common for fluorescence microscopy, equivalent multiplexable gene reporters for electron microscopy (EM) are still scarce. Here, by installing a variable number of fixation-stable metal-interacting moieties in the lumen of encapsulin nanocompartments of different sizes, we developed a suite of spherically symmetric and concentric barcodes (EMcapsulins) that are readable by standard EM techniques. Six classes of EMcapsulins could be automatically segmented and differentiated. The coding capacity was further increased by arranging several EMcapsulins into distinct patterns via a set of rigid spacers of variable length. Fluorescent EMcapsulins were expressed to monitor subcellular structures in light and EM. Neuronal expression in Drosophila and mouse brains enabled the automatic identification of genetically defined cells in EM. EMcapsulins are compatible with transmission EM, scanning EM and focused ion beam scanning EM. The expandable palette of genetically controlled EM-readable barcodes can augment anatomical EM images with multiplexed gene expression maps.

Original languageEnglish
Pages (from-to)1734-1745
Number of pages12
JournalNature Biotechnology
Volume41
Issue number12
DOIs
StatePublished - Dec 2023
Externally publishedYes

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