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. 2020 Oct;75(10):2548-2561.
doi: 10.1111/all.14307. Epub 2020 Jul 6.

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

Borja Callejas-Díaz  1   2 , Guerau Fernandez  3 , Mireya Fuentes  1   2 , Asunción Martínez-Antón  1   4 , Isam Alobid  1   2   5 , Jordi Roca-Ferrer  1   2 , César Picado  1   2   6 , Valeria Tubita  1 , Joaquim Mullol  1   2   5
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Integrated mRNA and microRNA transcriptome profiling during differentiation of human nasal polyp epithelium reveals an altered ciliogenesis

Borja Callejas-Díaz et al. Allergy. 2020 Oct.

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Air-liquid Interface (ALI) 3D in vitro model; Ciliogenesis; basal stem; miR34 and miR449; microRNA epigenetic regulation; progenitor cells (BSCs).

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References

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