Revisiting primary cilia
Revisiting primary ciliaWe are very happy to see that the HPA primary cilia research by Hansen et al., published in Cell in November, has been recognized as 'setting a new standard for understanding ciliary function and its role in health and disease'. The recent research highlight published in Nature Signal Transduction and Targeted Therapy praises the HPA work as fundamentally transformative for ciliary biology. The original HPA study, which manually annotated close to 20,000 confocal images and analyzed over 128,000 individual primary cilia across three cell types, represents three years of continuous microscopy-based analysis by the HPA subcellular team. The commentary emphasizes several key advances achieved by the HPA team's antibody-based spatial proteomics approach, saying that it provided "significant advantages over previous proximity-labeling methods" and enabled unprecedented resolution of single-cilium diversity that cannot be achieved with traditional bulk population approaches. Chiong et al. highlights the high degree of variability in protein composition observed in primary cilia both across cell types as well as between individual cilia of a single cell type, including a deep and complex set of signalling components (Fig. 1). The authors conclude that "The work fundamentally reconceptualizes the cilium as a customizable signaling center", encouraging further research into the mechanisms behind this diversification and the impact on cilia-dependent signaling outputs. Furthermore, the commentary highlights the clinical potential of the research, noting that the atlas "offers a new approach to identifying candidate disease genes in undiagnosed patients with multisystem disorders associated with ciliopathies", emphasizing how the work opens new avenues for diagnosis of rare genetic conditions. Overall, the study on primary cilia demonstrates that even though cell- and organelle biology has been studied for many decades, there remain unexplored territories that can now be mapped through recent advances in technologies like spatial proteomics. Read the Nature Signal Transduction & Targeted Therapy commentary |