Zhong Jing, Gao Rong-Rong, Zhang Xin, Yang Jia-Xin, Liu Yang, Ma Jinjin, Chen Qi
Center for Cell Lineage Atlas, CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, 510530, China.
University of Chinese Academy of Sciences, Beijing, China.
Cell Regen. 2025 Mar 23;14(1):10. doi: 10.1186/s13619-025-00223-3.
The formation of a blood vessel network is crucial for organ development and regeneration. Over the past three decades, the central molecular mechanisms governing blood vessel growth have been extensively studied. Recent evidence indicates that vascular endothelial cells-the specialized cells lining the inner surface of blood vessels-exhibit significant heterogeneity to meet the specific needs of different organs. This review focuses on the current understanding of endothelial cell heterogeneity, which includes both intra-organ and inter-organ heterogeneity. Intra-organ heterogeneity encompasses arterio-venous and tip-stalk endothelial cell specialization, while inter-organ heterogeneity refers to organ-specific transcriptomic profiles and functions. Advances in single-cell RNA sequencing (scRNA-seq) have enabled the identification of new endothelial subpopulations and the comparison of gene expression patterns across different subsets of endothelial cells. Integrating scRNA-seq with other high-throughput sequencing technologies promises to deepen our understanding of endothelial cell heterogeneity at the epigenetic level and in a spatially resolved context. To further explore human endothelial cell heterogeneity, vascular organoids offer powerful tools for studying gene function in three-dimensional culture systems and for investigating endothelial-tissue interactions using human cells. Developing organ-specific vascular organoids presents unique opportunities to unravel inter-organ endothelial cell heterogeneity and its implications for human disease. Emerging technologies, such as scRNA-seq and vascular organoids, are poised to transform our understanding of endothelial cell heterogeneity and pave the way for innovative therapeutic strategies to address human vascular diseases.
血管网络的形成对于器官发育和再生至关重要。在过去三十年中，调控血管生长的核心分子机制已得到广泛研究。最近的证据表明，血管内皮细胞（即血管内表面衬里的特化细胞）表现出显著的异质性，以满足不同器官的特定需求。本综述重点关注目前对内皮细胞异质性的理解，其中包括器官内和器官间的异质性。器官内异质性包括动静脉和尖端-柄部内皮细胞特化，而器官间异质性是指器官特异性转录组图谱和功能。单细胞RNA测序（scRNA-seq）技术的进步使得能够识别新的内皮亚群，并比较不同内皮细胞亚群之间的基因表达模式。将scRNA-seq与其他高通量测序技术相结合，有望在表观遗传水平和空间解析背景下加深我们对内皮细胞异质性的理解。为了进一步探索人类内皮细胞异质性，血管类器官为在三维培养系统中研究基因功能以及使用人类细胞研究内皮-组织相互作用提供了强大工具。开发器官特异性血管类器官为揭示器官间内皮细胞异质性及其对人类疾病的影响提供了独特机会。诸如scRNA-seq和血管类器官等新兴技术有望改变我们对内皮细胞异质性的理解，并为解决人类血管疾病的创新治疗策略铺平道路。
