近日，加拿大多伦多大学教授Thomas Wälchl及其研究小组绘制了跨越发育、成年和疾病的人类脑血管单细胞图谱。这一研究成果于2024年7月10日发表在国际顶尖学术期刊《自然》上。

小组对来自68名人类胎儿和成人患者的117个样本的606380个新鲜分离的内皮细胞、血管周围细胞和其他组织来源的细胞进行了单细胞RNA测序分析，以构建发育中的胎儿、成人对照和患病的人类脑血管系统的分子图谱。研究小组确定了健康胎儿和成人大脑血管系统的广泛分子异质性，以及五种血管依赖性中枢神经系统(CNS)病理，包括脑肿瘤和脑血管畸形。

课题组人员发现了动静脉分化的改变和重新激活的胎儿，以及病变血管中保守的失调基因和途径。病理性内皮细胞表现出中枢神经系统特异性的丧失，并显示MHC II类分子上调，表明中枢神经系统内皮细胞的非典型特征。细胞-细胞相互作用分析预测了大量内皮-血管周围细胞配体-受体交流，包括免疫相关和血管生成途径，从而揭示了内皮在脑神经血管单位信号网络中的核心作用。

他们的单细胞脑图谱提供了对发育中、成人/对照和患病人类脑血管系统的分子结构和异质性的见解，并为未来的研究提供了有力的参考。

据了解，广泛的脑病理严重依赖于脉管系统，脑血管疾病是世界范围内死亡的主要原因。然而，人类大脑血管的细胞和分子结构仍然不完全清楚。

附：英文原文

Title: Single-cell atlas of the human brain vasculature across development, adulthood and disease

Author: Wlchli, Thomas, Ghobrial, Moheb, Schwab, Marc, Takada, Shigeki, Zhong, Hang, Suntharalingham, Samuel, Vetiska, Sandra, Gonzalez, Daym Rodrigues, Wu, Ruilin, Rehrauer, Hubert, Dinesh, Anuroopa, Yu, Kai, Chen, Edward L. Y., Bisschop, Jeroen, Farnhammer, Fiona, Mansur, Ann, Kalucka, Joanna, Tirosh, Itay, Regli, Luca, Schaller, Karl, Frei, Karl, Ketela, Troy, Bernstein, Mark, Kongkham, Paul, Carmeliet, Peter, Valiante, Taufik, Dirks, Peter B., Suva, Mario L., Zadeh, Gelareh, Tabar, Viviane, Schlapbach, Ralph, Jackson, Hartland W., De Bock, Katrien, Fish, Jason E., Monnier, Philippe P., Bader, Gary D., Radovanovic, Ivan

Issue&Volume: 2024-07-10

Abstract: A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood1. Here we performed single-cell RNA sequencing analysis of 606,380 freshly isolated endothelial cells, perivascular cells and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We identify extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across five vascular-dependent central nervous system (CNS) pathologies, including brain tumours and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell–cell interaction analyses predict substantial endothelial-to-perivascular cell ligand–receptor cross-talk, including immune-related and angiogenic pathways, thereby revealing a central role for the endothelium within brain neurovascular unit signalling networks. Our single-cell brain atlas provides insights into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies.

DOI: 10.1038/s41586-024-07493-y

Source: https://www.nature.com/articles/s41586-024-07493-y