Integrated mRNA and microRNA transcriptome profiling during differentiation of human nasal polyp epithelium reveals an altered ciliogenesis

다국어 초록 (Multilingual Abstract)

Human adult basal stem/progenitor cells (BSCs) obtained from chronic rhinosinusitis with nasal polyps (CRSwNP) when differentiated in an air‐liquid interface (ALI) usually provide a pseudostratified airway epithelium with similar abnormalities than original in vivo phenotype. However, the intrinsic mechanisms regulating this complex process are not well defined and their understanding could offer potential new therapies for CRSwNP (incurable disease).
We performed a transcriptome‐wide analysis during in vitro mucociliary differentiation of human adult BSCs from CRSwNP, compared to those isolated from control nasal mucosa (control‐NM), in order to identify which key mRNA and microRNAs are regulating this complex process in pathological and healthy conditions.
A number of genes, miRs, biological processes, and pathways were identified during mucociliary differentiation of both CRSwNP and control‐NM epithelia, and notably, we have demonstrated for the first time that genetic transcriptional program responsible of ciliogenesis and cilia function is significantly impaired in CRSwNP epithelium, presumably produced by an altered expression of microRNAs, particularly of those miRs belonging to mir‐34 and mi‐449 families.
This study provides for the first time a novel insight into the molecular basis of sinonasal mucociliary differentiation, demonstrating that transcriptome related to ciliogenesis and cilia function is significantly impaired during differentiation of CRSwNP epithelium due to an altered expression of microRNAs.
This study provides an insight into the molecular basis of sinonasal mucociliary differentiation. mRNA and microRNA transcriptome profiling reveals an altered ciliogenesis in CRSwNP compared to control‐NM. Altered ciliogenesis during mucociliary differentiation may be related to the lack of expression of microRNAs from the mir‐34 and mir‐449 families in CRSwNP epithelium.
Abbreviations: ALI, air‐liquid interface cell culture system; BSCs, basal stem‐progenitor cells; control‐NM, control nasal mucosa; miR, microRNA; RSwNP, chronic rhinosinusitis with nasal polyps.