Novel Approach Combining Transcriptional and Evolutionary Signatures to Identify New Multiciliation Genes.

Audrey Defosset,Olivier Poch,Odile Lecompte,Arnaud Kress,Yannis Nevers,Dorine Merlat,Laetitia Poidevin

doi:10.3390/genes12091452

Abstract

Multiciliogenesis is a complex process that allows the generation of hundreds of motile cilia on the surface of specialized cells, to create fluid flow across epithelial surfaces. Dysfunction of human multiciliated cells is associated with diseases of the brain, airway and reproductive tracts. Despite recent efforts to characterize the transcriptional events responsible for the differentiation of multiciliated cells, a lot of actors remain to be identified. In this work, we capitalize on the ever-growing quantity of high-throughput data to search for new candidate genes involved in multiciliation. After performing a large-scale screening using 10 transcriptomics datasets dedicated to multiciliation, we established a specific evolutionary signature involving Otomorpha fish to use as a criterion to select the most likely targets. Combining both approaches highlighted a list of 114 potential multiciliated candidates. We characterized these genes first by generating protein interaction networks, which showed various clusters of ciliated and multiciliated genes, and then by computing phylogenetic profiles. In the end, we selected 11 poorly characterized genes that seem like particularly promising multiciliated candidates. By combining functional and comparative genomics methods, we developed a novel type of approach to study biological processes and identify new promising candidates linked to that process.

Highlights

Multiciliogenesis is a complex process that allows the generation of hundreds of motile cilia on the surface of specialized cells, to create fluid flow across epithelial surfaces
Eight datasets comprised of results from ten transcriptomics experiments specific to multiciliation (Table 1) were retrieved from the Gene Expression Omnibus (GEO) database of the NCBI [37] for our functional genomics analysis
To expand our current knowledge regarding the generation and maintenance of multiciliated cells (MCCs), we combined functional genomics and comparative genomics data in order to highlight genes that were likely to be involved in this process

Summary

Introduction

Multiciliogenesis is a complex process that allows the generation of hundreds of motile cilia on the surface of specialized cells, to create fluid flow across epithelial surfaces. After performing a large-scale screening using 10 transcriptomics datasets dedicated to multiciliation, we established a specific evolutionary signature involving Otomorpha fish to use as a criterion to select the most likely targets. Combining both approaches highlighted a list of 114 potential multiciliated candidates. In humans, multiciliated cells (MCCs) are found in the spinal cord and the brain ventricles, where they direct cerebrospinal fluid flow in the respiratory tract and play an important role in mucus clearance, as well as in both male and female reproductive tracts (reviewed in [3]).

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Methods

Results