Human Single-cell Atlas Analysis Reveals Heterogeneous Endothelial Signaling
Year: 2026
Type: article
Abstract: Endothelial cells (ECs) play complex roles across tissues and vessel types. Yet, systematic investigations of EC heterogeneity in the combined context of vessel type and tissue microenvironment are still largely lacking. We integrated over three million single cells from single-cell RNA-seq datasets in 15 human tissues. We found that ECs in some tissues (e.g., heart and kidney) exhibited greater tissue specificity, whereas others showed greater vessel specificity. We developed a computational pipeline to analyze cell-cell communications (CCC) mediated by metabolites or proteins to explore microenvironmental regulation. Interestingly, our results showed that CCC events involving ECs varied vastly across tissues, highlighting tissue-specific EC interactions. Using topic modeling, we identified CCC patterns, termed CCC topics, representing metabolite- and protein-mediated interactions between ECs and other tissue-resident cells. Most CCC topics showed high tissue specificity, potentially explaining the microenvironmental regulation of EC heterogeneity. The work systematically investigates EC heterogeneity and provides insights into its regulation across diverse tissue microenvironments. The script to reproduce all analyses in this study is available at https://github.com/zhuzimoo/EC_project.
Authors: Zimo Zhu, Rongbin Zheng, Yang Yu, Lili Zhang, Kaifu Chen
Institutions: Boston Children's Hospital, Harvard University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,850
Awards: Computational epigenetics modeling of cell identity genes, Role of S-nitrosylation in Transdifferentiation, G2084212741, Reversal of Heart Failure: Role of Vascular Recovery, A novel role for EZH2 in A-to-I RNA editing in prostate cancer, Transcription Factor 4 Maintain Endothelial identity to Oppose Heart Failure, Bioinformatics Techniques to Analyze Dynamic Changes of 3D Genome, Computational Technology for Single-Cell Functional Genomics, Targeting Endothelial Epsins to Ameliorate Myocardial Ischemia
OpenAlex ID: W7139979874
