Probing molecular diversity of brain cells with chemically modified aptamers

ABSTRACT: We developed a volumetric correlated light and electron microscopy (CLEM) approach that uses slow off-rate modified aptamers (SOMAmers) for fluorescence labeling of cells in ultrastructurally reconstructable electron micrographs. The small size of aptamers enables intracellular labeling in fixed brain tissue without detergent permeabilization, thereby preserving tissue ultrastructure and allowing high-resolution electron microscopy imaging and accurate cellular segmentation. This method enables labeling of a wide range of molecular biomarkers, providing a powerful strategy to integrate molecular information with volumetric electron microscopy datasets. As a result, it facilitates molecularly annotated ultrastructural studies of complex tissues, including investigations of neural circuits. To ensure that the aptamers used in this method bind specifically to their intended protein targets, we validated target binding using pull-down mass spectrometry. These results were further confirmed through complementary approaches including genetic correlation analyses, proximity extension assays, and comparisons with commercial antibody labeling.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Xiaotang Lu  

LAB HEAD: Xiaotang Lu

PROVIDER: PXD075602 | Pride | 2026-04-17

REPOSITORIES: Pride