Sun Yi, Xu Haoyang, Zhu Yanze, Rao Yamin, Fan Xindong, Wang Zhenfeng, Gu Hao, Yue Xiaojie, Zhao Xiong, Su Lixin, Cai Ren
Department of Interventional Therapy, Multidisciplinary Team of Vascular Anomalies, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Dermatol Sci. 2025 May;118(2):66-75. doi: 10.1016/j.jdermsci.2025.02.005. Epub 2025 Feb 24.
Extracranial arteriovenous malformations (eAVMs) are rare congenital vascular anomalies consisting of abnormal artery-vein bypass with no intervening capillary network, and can lead to disability and death. The critical genetic determination factors and key transcriptional pathways of the eAVMs genesis process are still unclear.
To generate an overview of the molecular information within eAVMs at the single-cell level.
We performed single-cell RNA sequencing (scRNA-seq) on nine samples of eAVMs receiving a confirmatory histopathologic evaluation from a board-certified dermatopathologist and two nonlesional tissue sample controls. 10x Visium spatial transcriptomics (ST) was performed on one eAVM to spatially localize heterogeneous cells and profile the gene expression dynamics of the cells in their morphological context. The scRNA-seq and ST data were integrated and analyzed to further query for spatially restricted mapping of intrapopulation heterogeneous cells.
We identified different cell states of endothelial cells (ECs), perivascular cells and immune cells in eAVMs, uncovered the presence of MAFB+ nidus ECs, characterized mesenchymal activation in ECs, and identified transcriptional variation within perivascular cells and the presence of smooth muscle-like pericytes in eAVMs. Dysregulated cell to cell interactions among ECs, perivascular cells and immune cells that are associated with eAVMs, including those involving MDK, VEGF, ANGPT, SEMA3 and GALECTIN-9 were cataloged. Together, our results depicted the heterogeneity underlying cell function and interaction of eAVMs at a single-cell resolution.
We present a comprehensive picture of the cell-resolution atlas that describes the transcriptomic heterogeneity underlying cell function and interaction in eAVMs.
颅外动静脉畸形（eAVM）是罕见的先天性血管异常，由异常的动静脉分流组成，其间无毛细血管网络，可导致残疾和死亡。eAVM发生过程的关键遗传决定因素和关键转录途径仍不清楚。
在单细胞水平上概述eAVM内的分子信息。
我们对9个经皮肤科病理专家确诊的eAVM样本和2个非病变组织样本对照进行了单细胞RNA测序（scRNA-seq）。对1个eAVM样本进行了10x Visium空间转录组学（ST）分析，以在空间上定位异质性细胞，并描绘细胞在其形态背景下的基因表达动态。对scRNA-seq和ST数据进行整合和分析，以进一步探寻群体内异质性细胞的空间受限图谱。
我们在eAVM中鉴定出内皮细胞（EC）、血管周围细胞和免疫细胞的不同细胞状态，发现了MAFB+巢状EC的存在，描述了EC中的间充质激活，并确定了血管周围细胞内的转录变异以及eAVM中平滑肌样周细胞的存在。对与eAVM相关的EC、血管周围细胞和免疫细胞之间失调的细胞间相互作用进行了分类，包括涉及MDK、VEGF、ANGPT、SEMA3和GALECTIN-9的相互作用。总之，我们的结果以单细胞分辨率描绘了eAVM细胞功能和相互作用的异质性。
我们展示了一个细胞分辨率图谱的全貌，该图谱描述了eAVM中细胞功能和相互作用的转录组异质性。
