Congratulations to Systems Biology Ireland (SBI) researchers Dr Oleksii Rukhlenko, Dr Philipp Junk, Anna Tuliakova and Prof Boris Kholodenko together with their international collaborators from Prof Martin Schwartz's team at Yale School of Medicine on their latest paper published in the January issue of Science Advances titled “cSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling”.
Fluid shear stress (FSS) from blood flow sensed by vascular endothelial cells (ECs) determines vessel behavior, but regulatory mechanisms are only partially understood. We used cell state transition assessment and regulation (cSTAR), a powerful computational method, to elucidate EC transcriptomic states under low shear stress (LSS), physiological shear stress (PSS), high shear stress (HSS), and oscillatory shear stress (OSS) that induce vessel inward remodeling, stabilization, outward remodeling, or disease susceptibility, respectively. Combined with a publicly available database on EC transcriptomic responses to drug treatments, this approach inferred a regulatory network controlling EC states and made several notable predictions. Particularly, inhibiting cell cycle–dependent kinase (CDK) 2 was predicted to initiate inward remodeling and promote atherogenesis. In vitro, PSS activated CDK2 and induced late G1 cell cycle arrest. In mice, EC deletion of CDK2 triggered inward artery remodeling, pulmonary and systemic hypertension, and accelerated atherosclerosis. These results validate use of cSTAR and identify key determinants of normal and pathological artery remodeling.
Read the full paper here: https://doi.org/10.1126/sciadv.ado9970