2026-10-14T19:29:16Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33944587 2026-09-20T07:17:34Z category_27241 item_type_3 month_year_09_2026

Sexually Dimorphic Transdifferentiation of Endothelial Cells in Atherosclerosis Qing Lyu (23156050) Other health sciences not elsewhere classified Sexually dimorphism Lineage tracing Endothelial cells Atherosclerosis <p dir="ltr">Sex differences in atherosclerosis are clinically recognized, but the underlying mechanisms remain incompletely understood. In this study, we investigated sex-specific endothelial cell (EC) states and cell fate trajectories in atherosclerosis. Both male and female <i>Apoe</i>^{<em>−/−</em>}<i>/Cdh5-CreER</i>^<em>T2</em><i>/Rosa26-mTmG</i> mice were generated for EC-specific lineage-tracing and were fed a high-fat diet (HFD) to establish hypercholesterolemia and atherosclerosis. Here we show that single-nucleus RNA sequencing (snRNA-seq) of plaque-bearing aortae identified nine sex-biased EC subpopulations, including capillary, lymphatic, <i>Sox17</i>, <i>Myh11</i>, <i>Mki67</i>, and <i>Ly6a</i> ECs enriched in females, and <i>Col8a1</i> and <i>Fmo2</i> ECs enriched in males. GeneTrajectory and lineage tracing indicated that approximately one quarter of GFP⁺ EC-lineage cells acquired adipocyte-like, SMC-like, or fibroblast-like states, with female-biased EC-to-SMC-like and male-biased EC-to-adipocyte-like transitions.Regulatory network analysis using <i>pySCENIC</i> implicated <i>Klf2</i> and <i>Creb5</i> in EC fate decisions in the context of atherosclerosis. These findings identify sex-specific EC-lineage trajectories associated with distinct plaque phenotypes and nominate candidates for sex-informed therapeutic investigation.</p> 2026-09-20T07:17:34Z Dataset Dataset 10.6084/m9.figshare.33944587.v1 https://figshare.com/articles/dataset/Sexually_Dimorphic_Transdifferentiation_of_Endothelial_Cells_in_Atherosclerosis/33944587 CC BY 4.0