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

The 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.