Abstract
Cilia are cell organelles that play important roles in cell motility, sensory and developmental functions and are involved in a range of human diseases, known as ciliopathies. Here, we search for novel human genes related to cilia using a strategy that exploits the previously reported tendency of cell type-specific genes to be coexpressed in the transcriptome of complex tissues. Gene coexpression networks were constructed using the noise-resistant WGCNA algorithm in 12 publicly available microarray datasets from human tissues rich in motile cilia: airways, fallopian tubes and brain. A cilia-related coexpression module was detected in 10 out of the 12 datasets. A consensus analysis of this module's gene composition recapitulated 297 known and predicted 74 novel cilia-related genes. 82% of the novel candidates were supported by tissue-specificity expression data from GEO and/or proteomic data from the Human Protein Atlas. The novel findings included a set of genes (DCDC2, DYX1C1, KIAA0319) related to a neurological disease dyslexia suggesting their potential involvement in ciliary functions. Furthermore, we searched for differences in gene composition of the ciliary module between the tissues. A multidrug-and-toxin extrusion transporter MATE2 (SLC47A2) was found as a brain-specific central gene in the ciliary module. We confirm the localization of MATE2 in cilia by immunofluorescence staining using MDCK cells as a model. While MATE2 has previously gained attention as a pharmacologically relevant transporter, its potential relation to cilia is suggested for the first time. Taken together, our large-scale analysis of gene coexpression networks identifies novel genes related to human cell cilia.
Highlights
Cilia are microtubule-rich organelles which protrude from cell surface and play important roles in motility, sensory perception [1] and development [2] in a wide range of eukaryotes including human
It was recently found that gene coexpression networks generated from tissue-level data include modules related to universal cellular functions and those corresponding to individual cell types [19]
We explored the transcriptomes of brain, airways and fallopian tubes, and identified a coexpression module related to cells with motile cilia in these tissues
Summary
Cilia are microtubule-rich organelles which protrude from cell surface and play important roles in motility, sensory perception [1] and development [2] in a wide range of eukaryotes including human. In the adult human body, epithelial cells with motile cilia are highly abundant in airways, reproductive tracts and specific brain regions [3]. In these tissues, motile cilia are important for clearance of mucosa (airways), transport of oocytes (fallopian tubes) and circulation of cerebrospinal fluid (brain) [4]. Many human tissues contain cells with a single non-motile cilium (called a ‘primary’ cilium) [5], airways, fallopian tubes and specific brain regions are peculiar in containing epithelial cells with numerous and motile cilia [4]. Identification of proteins that are involved in cilia biogenesis and motion is important for understanding how cilia function in health and disease [3,7]
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