Constant inhibition of local BMP signaling contributes to recovery of mucociliary epithelium from Tracheobronchopathia Osteochondroplastica (TO)-associated pathophysiology via basal cell restoration

Tracheobronchial basal cells have been found to undergo persistent functional changes, via acting as a local repository for BMP signaling elements, thereby play a driven role in TO pathogenesis. Although it would be unlikely to fundamentally correct cell fate alteration, because of epigenetic changes occurred, partial restoration of epithelial physiology may be achieved by braking self-amplifying BMP signaling loop. To investigate the effect of BMP inhibition on TO-derived basal cells, ALI structures derived from routine differentiation without Noggin treatment and modified differentiation with constant BMP inhibition were subjected to RNA-sequencing. While a differentiation pattern of 3538 genes up-regulated and 2109 genes down-regulated (>2-fold or <-2-fold, p<0.05) upon routine differentiation of a typical TO-derived pedigree, differentiation in the presence of BMP inhibition resulted in an up-regulation of 4101 genes and down-regulation of 2337 genes (equivalent cutoff as above). Among those 1554 genes with significantly increased expression on ALI under BMP inhibition, a major enrichment shown up in categories related to cilium assembly and function, and an up-turned Smoothened signaling were detected. In contrast, 482 genes with decreased expression under BMP inhibition were mainly fallen into categories related to biomineral tissue development. These data suggest that constant repression of local BMP signaling has a favorable effect, to some extent, on functional rescue of pathological basal cells. Samples at stem cell state, differentiated without BMP inhibitor treatment and differentiated along BMP inhibition were analyzed by RNA-Seq, in singleton.