Single-cell RNA analysis reveals the cell atlas of human intracranial aneurysm and rupture-related inflammation features

Background Intracranial aneurysms (IA) is a common condition and may ultimately result in life-threatening hemorrhagic strokes. A precise understanding of the cellular and gene expression perturbations in human IA tissue may enlighten additional therapeutics for unruptured IA. Methods A total of 21,332 qualified cells were obtained from four cell-sparse ruptured and unruptured human IA tissues. Detailed cell atlas and dynamics, gene expression perturbations, and inflammation features were thoroughly investigated using multiple machine learning-based algorithms. Results Endothelial cells, smooth muscle cells (SMCs), fibroblasts and, for the first time, pericytes have been identified in human IA tissue. A significant proportion of immune cells are also identified, with the number of monocyte/macrophages and neutrophils being notably higher in ruptured IA. By leveraging external datasets, macrophages characterized by transcriptional activation of NF-κB and HIVEP2 is most strongly associated with IA rupture. Interestingly, the recruitment and activation of macrophages and their functional characteristics in terms of TNFα and chemokine production remain consistent between unruptured and ruptured IA. Conclusions This study provides insights into the pathophysiology and molecular underpinnings of the IA wall and may motivate novel therapeutic options for unruptured IA. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Academic Excellence Development 1-3-5 Project of Sichuan University, West China Hospital (2018HXFH007), Sichuan Provincial Science and Technology Plan Program (2022YFS0320), Sichuan Provincial Science and Technology Plan Program (2022YFS0013). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Ethics Review Committee of West China Hospital, Sichuan University, and was performed in accordance with Good Clinical Practice guidelines and the 1964 Helsinki Declaration and its later amendments. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The source code and collated gene expression profile can be obtained from the corresponding author upon reasonable request. * CCA : canonical correlation analysis DC : dendritic cell IA : intracranial aneurysm MAIT : mucosal associated invariant T MNN : mutual nearest neighbor PCA : principal component analysis SMC : smooth muscle cell SAH : spontaneous subarachnoid hemorrhage ssGSEA : single-sample gene set enrichment analysis WGCNA : weighted gene co-expression network analysis.