Human and murine fibroblast single cell transcriptomics reveals fibroblast clusters are differentially affected by ageing, and serum cholesterol

Aims Specific fibroblast markers and in-depth heterogeneity analysis are currently lacking, hindering functional studies in cardiovascular diseases (CVDs). Here, we established cell-type markers and heterogeneity in murine and human arteries and studied the adventitial fibroblast response to CVD and its risk factors hypercholesterolaemia and ageing. Methods and results Murine aorta single-cell RNA-sequencing analysis of adventitial mesenchymal cells identified fibroblast-specific markers. Immunohistochemistry and flow cytometry validated platelet-derived growth factor receptor alpha (PDGFRA) and dipeptidase 1 (DPEP1) across human and murine aorta, carotid, and femoral arteries, whereas traditional markers such as the cluster of differentiation (CD)90 and vimentin also marked transgelin+ vascular smooth muscle cells. Next, pseudotime analysis showed multiple fibroblast clusters differentiating along trajectories. Three trajectories, marked by CD55 (Cd55+), Cxcl chemokine 14 (Cxcl14+), and lysyl oxidase (Lox+), were reproduced in an independent RNA-seq dataset. Gene ontology (GO) analysis showed divergent functional profiles of the three trajectories, related to vascular development, antigen presentation, and/or collagen fibril organization, respectively. Trajectory-specific genes included significantly more genes with known genome-wide associations (GWAS) to CVD than expected by chance, implying a role in CVD. Indeed, differential regulation of fibroblast clusters by CVD risk factors was shown in the adventitia of aged C57BL/6J mice, and mildly hypercholesterolaemic LDLR KO mice on chow by flow cytometry. The expansion of collagen-related CXCL14+ and LOX+ fibroblasts in aged and hypercholesterolaemic aortic adventitia, respectively, coincided with increased adventitial collagen. Immunohistochemistry, bulk, and single-cell transcriptomics of human carotid and aorta specimens emphasized translational value as CD55+, CXCL14+ and LOX+ fibroblasts were observed in healthy and atherosclerotic specimens. Also, trajectory-specific gene sets are differentially correlated with human atherosclerotic plaque traits. Conclusion We provide two adventitial fibroblast-specific markers, PDGFRA and DPEP1, and demonstrate fibroblast heterogeneity in health and CVD in humans and mice. Biological relevance is evident from the regulation of fibroblast clusters by age and hypercholesterolaemia in vivo, associations with human atherosclerotic plaque traits, and enrichment of genes with a GWAS for CVD

Dismantling SecureMemory, CryptoMemory and CryptoRF

Contains fulltext : 83892.pdf (publisher's version ) (Open Access

Logical Formalisation and Analysis of the Mifare Classic Card in PVS

Contains fulltext : 83531.pdf (preprint version ) (Open Access)14 p

Crossing borders: Security and privacy issues of the European e-passport

The first generation of European e-passports will be issued in 2006. We discuss how borders are crossed regarding the security and privacy erosion of the proposed schemes, and show which borders need to be crossed to improve the security and the privacy protection of the next generation of e-passports. In particular we discuss attacks on Basic Access Control due to the low entropy of the data from which the access keys are derived, we sketch the European proposals for Extended Access Control and the weaknesses in that scheme, and show how fundamentally different design decisions can make e-passports more secure

Dismantling MIFARE Classic

Contains fulltext : 72188.pdf (publisher's version ) (Closed access)Computer security - ESORICS 2008 : 13th European Symposium on Research in Computer Security, 6 oktober 200