Expression profiling of tracheobronchial basal cells derived from patients with Tracheobronchopathia Osteochondroplastica (TO), before and after in vitro differentiation. Expression profiling of tracheobronchial basal cells derived from patients with Tracheobronchopathia Osteochondroplastica (TO), before and after in vitro differentiation

Next-generation sequencing of mRNA extracted from immature tracheobronchial basal cells and their differentiated structures from air-liquid interface (ALI) was performed to quantitatively analyze TO-associated changes at transcriptional levels. RNA-Seq data revealed distinct expression profiles and divergent fate commitments between normal tissue-derived and TO lesion region-derived basal cells. In particular, there were 339 genes up-regulated at stem cell state and 1266 up-regulated upon differentiation (cutoff at fold change>2, p<0.05) in TO, whilst 173 TO-associated down-regulated genes and 1646 genes with reduced expression (cutoff at fold change<-2, p<0.05) were detected before and after differentiation respectively, compared to normal controls. Our results show that TO-derived basal cells, although exhibit high similarities on clone morphology and key marker staining, are transcriptionally different from normal tissue-derived counterpart and possess altered multipotency evidenced by transcriptome characterization. To further evaluate airway basal cell conditions in lesion-free regions of TO patients, RNA-Seq data was generated on cultured TBBCs derived from patient-matched (PM) relatively normal regions, and their ALI differentiated structures. Compared to stem cell state, there were 3314 genes induced in expression whilst 1627 down-regulated in the process of PM-TBBCs differentiation. Distinct differentiation-induced gene expression patterns were detected across TO patients, indicating a change of basal cell condition from normal mucociliary-committed status to a more disease-prone, inflammatory state during TO progression, and such basal cell alteration appeared prior to nodule formation. Overall design: RNA-Seq data was generated on normal tissue-derived （donors n=7）, TO PM-derived and TO lesion region-derived basal cell clones (donors n=6); for differentiated state, data was generated on normal cell-derived and TO cell-derived ALIs, corresponding to sample cases of which basal cell clones were subjected to RNA-Seq.