Research articleUnspecific labelling of oligodendrocytes by sulforhodamine 101 depends on astrocytic uptake via the thyroid hormone transporter OATP1C1 (SLCO1C1)

•In hippocampus oligodendrocytes are labeled with sulforhodamine 101.•The astrocytic thyroid hormone transporter OATP1C1 (SLCO1C1) is required for oligodendrocyte labeling.•Sulforhodamine 101 is not specific enough to be used as an unequivocal cell marker.

sThe red fluorescent dye Sulforhodamine 101 (SR101) is often used as a marker for astrocytes, although variations of the staining protocol have been shown to influence the preferentially labeled cell type. Here we analyzed SR101-labeling of oligodendrocytes in the hippocampal slices preparation of PLP-EGFP mice. Using different staining protocols, we found robust SR101-labeled oligodendrocytes in the CA1 stratum radiatum of the hippocampus. Application of L-thyroxin, which is known to block SR101 transport into astrocytes via competitive inhibition of the multi-specific OATP1C1 (SLCO1C1) transporter, significantly reduced oligodendrocyte labeling. Since OATP1C1 is not expressed in oligodendrocytes, we conclude that oligodendrocyte labeling with SR101 requires SR101-uptake by astrocytes, which then diffuses to oligodendrocytes via heterotypic gap junctions of the pan-glial network. In summary, unequivocal identification of a particular cell type is not possible by SR101 only, hence caution is recommended when using SR101 in future studies.