title: Exploring the transcriptome of ciliated cells using in silico dissection of human tissues.
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.
authors.affiliation: A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Ivliev
authors.forename: Peter A C
authors.initials: PA
authors.lastname: 't Hoen
authors.forename: Willeke M C
authors.initials: WM
authors.lastname: van Roon-Mom
authors.forename: Dorien J M
authors.initials: DJ
authors.lastname: Peters
authors.forename: Marina G
authors.initials: MG
authors.lastname: Sergeeva
mesh_terms: D000465:Algorithms; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D002923:Cilia / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins; D030541:Databases, Genetic; D004285:Dogs; D004410:Dyslexia / Q000235:genetics*; D005187:Fallopian Tubes / Q000166:cytology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D040901:Proteomics / Q000379:methods*; D012137:Respiratory System / Q000166:cytology / Q000378:metabolism; D059467:Transcriptome
chemical_list: D003598:Cytoskeletal Proteins; C510451:DCDC2 protein, human; C478878:DNAAF4 protein, human; C500377:KIAA0319 protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D027701:Organic Cation Transport Proteins; C521870:SLC47A2 protein, human