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

Asymptotic solution and numerical simulation of homogeneous condensation in expansion cloud chambers

Asymptotic solution of homogeneous condensation in expansion cloud chambers in different droplet growth regimes is presented. In particular an exactly solvable droplet growth model ranging between the Hertz–Knudsen and continuum droplet growth laws is introduced. The distinct condensation zones in each droplet growth regime are identified by the asymptotic solution of the condensation rate equation and the results are compared with those of direct numerical simulations using the classical nucleation theory. Excellent qualitative agreement is reached despite some minor quantitative differences in some of the condensation zones arising from the nature of the asymptotic solution in these zones

On Mist Formation in Natural Gas

Mist formation that occurs during production, handling, and transport of natural gas is shown to be the result of non equilibrium thermodynamic processes. A simple analysis is presented of these nucleation and droplet growth phenomena in natural gas, and an estimate is given of the rate at which droplets are formed for typical process conditions. A model of droplet growth due to condensation is presented. The nucleation and condensation behaviour of two samples of a natural gas is investigated in a Wilson expansion cloud chamber for the initial pressure range of 5 to 50 bar and initial temperatures of 294-297 K (21-24°C). For a cooling rate of about 1 K/ms, a typical undercooling at the onset of condensation is found of 32 ý 3K and 60 ý 5K respectively for the two samples, which emphasizes the importance of non-equilibrium effects

On Mist Formation in Natural Gas Sur la formation de buée dans le gaz naturel

Mist formation that occurs during production, handling, and transport of natural gas is shown to be the result of non equilibrium thermodynamic processes. A simple analysis is presented of these nucleation and droplet growth phenomena in natural gas, and an estimate is given of the rate at which droplets are formed for typical process conditions. A model of droplet growth due to condensation is presented. The nucleation and condensation behaviour of two samples of a natural gas is investigated in a Wilson expansion cloud chamber for the initial pressure range of 5 to 50 bar and initial temperatures of 294-297 K (21-24°C). For a cooling rate of about 1 K/ms, a typical undercooling at the onset of condensation is found of 32 ý 3K and 60 ý 5K respectively for the two samples, which emphasizes the importance of non-equilibrium effects. La formation de buée au cours de la production, du maniement et du transport de gaz naturel est le résultat d'un déséquilibre thermodynamique. Une analyse simple de la nucléation et de la croissance des gouttelettes dans le gaz naturel est présentée. Une estimation du taux de formation dans de tels processus ainsi qu'un modèle de croissance des gouttelettes par condensation sont alors établis. La nucléation et la condensation de deux échantillons de gaz naturel ont été examinées dans une chambre d'expansion de Wilson dont les gammes de pression et de température initiales sont respectivement de 5 à 10 bar et de 294 à 297 K (21-24°C). Pour un taux de refroidissement de 1 K/ms, les valeurs de sous-refroidissement trouvées au moment de l'initialisation de la condensation sont respectivement pour les deux échantillons 32 ý 3K et 60 ý 5K, ce qui souligne l'importance des effets de déséquilibre