Frequent and biased odorant receptor (OR) re-selection in an olfactory placode-derived cell line.

Abstract

We previously characterized a clonal olfactory placode-derived cell line (OP6) as a model system for studying odorant receptor (OR) choice, where individual OP6 cells, similar to olfactory sensory neurons in vivo, transcribe one allele ("monoallelic") of one OR gene ("monogenic"). The OP6 cell line provides a unique opportunity to investigate intrinsic properties of OR regulation that cannot easily be investigated in vivo. First, whereas OR-expressing cells in vivo are post-mitotic, OP6 cells are immortalized, raising interesting questions about the stability of epigenetic states associated with OR selection/silencing as OP6 cells progress through the cell cycle. Second, OP6 cells have been isolated away from extrinsic developmental cues, and therefore, any long-term OR selection biases are likely to arise from intrinsic epigenetic states that persist in the absence of developmental context. In this study, we investigated OR re-selection frequency and selection biases within clonal OP6 cell populations. We found no evidence of OR stability through the cell cycle: our results were most consistent with OR re-selection events transpiring at least once per cell division, suggesting that chromatin states associated with OR selection in this system might not be maintained in the subsequent generation. In contrast, we found strong evidence for OR selection biases maintained over prolonged culturing across a diverse set of OP6 cell lineages, suggesting the persistence of intrinsic epigenetic states that advantage some OR loci over others. Together, our data suggest that in the absence of instructive cues, intrinsic epigenetic states influencing OR eligibility, but not those determining OR choice, might persist through the cell cycle.