Cilium induction triggers differentiation of glioma stem cells
Gladiola Goranci-Buzhala, Aruljothi Mariappan, Lucia Ricci‐Vitiani, Nataša Josipović, Simone Pacioni, Marco Gottardo, Johannes Ptok, Heiner Schaal, Giuliano Callaini, Krishnaraj Rajalingam, Brian David Dynlacht, Kamyar Hadian, Argyris Papantonis, Roberto Pallini, Jay Gopalakrishnan
Abstract
Glioblastoma multiforme (GBM) possesses glioma stem cells (GSCs) that promote self-renewal, tumor propagation, and relapse. Understanding the mechanisms of GSCs self-renewal can offer targeted therapeutic interventions. However, insufficient knowledge of GSCs' fundamental biology is a significant bottleneck hindering these efforts. Here, we show that patient-derived GSCs recruit elevated levels of proteins that ensure the temporal cilium disassembly, leading to suppressed ciliogenesis. Depleting the cilia disassembly complex components is sufficient to induce ciliogenesis in a subset of GSCs via relocating platelet-derived growth factor receptor-alpha (PDGFR-α) to a newly induced cilium. Importantly, restoring ciliogenesis enabled GSCs to switch from self-renewal to differentiation. Finally, using an organoid-based glioma invasion assay and brain xenografts in mice, we establish that ciliogenesis-induced differentiation can prevent the infiltration of GSCs into the brain. Our findings illustrate a role for cilium as a molecular switch in determining GSCs' fate and suggest cilium induction as an attractive strategy to intervene in GSCs proliferation.