Abstract
Cilia are complex microtubule-based organelles essential to a range of processes associated with embryogenesis and tissue homeostasis. Mutations in components of these organelles or those involved in their assembly may result in a diverse set of diseases collectively known as ciliopathies. Accordingly, many cilia-associated proteins have been described, while those distinguishing cilia subtypes are poorly defined. Here we set out to define genes associated with motile cilia in humans based on their transcriptional signature. To define the signature, we performed network deconvolution of transcriptomics data derived from tissues possessing motile ciliated cell populations. For each tissue, genes coexpressed with the motile cilia-associated transcriptional factor, FOXJ1, were identified. The consensus across tissues provided a transcriptional signature of 248 genes. To validate these, we examined the literature, databases (CilDB, CentrosomeDB, CiliaCarta and SysCilia), single cell RNA-Seq data, and the localisation of mRNA and proteins in motile ciliated cells. In the case of six poorly characterised signature genes, we performed new localisation experiments on ARMC3, EFCAB6, FAM183A, MYCBPAP, RIBC2 and VWA3A. In summary, we report a set of motile cilia-associated genes that helps shape our understanding of these complex cellular organelles.
Highlights
Cilia are complex microtubule-based organelles essential to a range of processes associated with embryogenesis and tissue homeostasis
Causative mutations leading to primary ciliary dyskinesia include those in genes encoding the motile ciliary components of radial spokes (RSPH1, RSPH9 and RSPH4A)[15,16], dynein arms, the outer dynein arm (DNAI1, DNAI2 and DNAH11)[17,18,19], proteins involved in their assembly (CCDC103, LRRC6 and ZMYND10)[20,21,22] and the key transcriptional regulator of motile ciliogenesis FOXJ123
The most relevant to the study of human cilia include: CentrosomeDB, a set of human genes encoding proteins that are localized in the centrosome, either as centrosome constituents or as centrosome visitors[33]; CilDB a database dedicated to proteins involved in centrioles, centrosomes, basal bodies, cilia and flagella in eukaryotes[34]; SysCilia a curated list of cilia genes many of which are associated with disease[35]; and CiliaCarta which employs a naive Bayesian classifier to predict cilia candidate genes across a diverse set of datasets[36]
Summary
Cilia are complex microtubule-based organelles essential to a range of processes associated with embryogenesis and tissue homeostasis. The most relevant to the study of human cilia include: CentrosomeDB, a set of human (and Drosophila) genes encoding proteins that are localized in the centrosome, either as centrosome constituents or as centrosome visitors[33]; CilDB a database dedicated to proteins involved in centrioles, centrosomes, basal bodies, cilia and flagella in eukaryotes[34]; SysCilia a curated list of cilia genes many of which are associated with disease[35]; and CiliaCarta which employs a naive Bayesian classifier to predict cilia candidate genes across a diverse set of datasets[36] These resources list between 303 and 3,376 genes and have greatly broadened our understanding of the complexity of cilia while attempting to define the role of these genes in the context of development, ciliogenesis and ciliopathies
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