A cell and transcriptome atlas of human arterial vasculature
Arterial segments show differing disease propensities, yet mechanisms remain unknown. We compiled a transcriptomic and spatial atlas of healthy human arterial cells across multiple segments to understand these differences. Arteries demonstrated a stereotyped pattern of cell-specific, segmental heterogeneity not captured by common marker genes. Arterial identities are encoded in fibroblast and smooth muscle cell (SMC) transcriptomes. Differentially expressed genes enrich for disease loci. Fibroblast gene expression enriches for a disproportionate number of disease loci, highlighting an underrecognized role for fibroblasts in disease risk. Cells of different segments cluster more by embryonic origin than anatomy. Global analysis of disease regulons in fibroblasts and SMCs identified developmental transcription factors that persist into adulthood, suggesting a functional role of these factors in disease. Lastly, the heterogeneity of non-coding transcriptomes rivals that of protein-coding transcriptomes. Differentially expressed lncRNAs enrich for genetic signals for vascular diseases, suggesting a role for lncRNAs in vascular disease.
Authors
- Huitong Shi
- Trieu Nguyen (ORCID: https://orcid.org/0000-0001-5647-1301)
- Michael P. Fischbein (ORCID: https://orcid.org/0000-0002-0638-2025)
- Juyong Brian Kim (ORCID: https://orcid.org/0000-0002-9675-2607)
- João P Monteiro (ORCID: https://orcid.org/0000-0001-6481-6875)
- Disha Sharma (ORCID: https://orcid.org/0000-0001-9486-2709)
- Matthew D. Worssam (ORCID: https://orcid.org/0000-0003-4391-5377)
- Yana Ryan
- Quanyi Zhao (ORCID: https://orcid.org/0000-0001-9849-4528)
- Thomas Quertermous (ORCID: https://orcid.org/0000-0002-7645-9067)
- Ramendra Kundu (ORCID: https://orcid.org/0000-0001-7696-8067)
- Brian T. Palmisano (ORCID: https://orcid.org/0000-0002-2140-1060)
- Albert J Pedroza (ORCID: https://orcid.org/0000-0001-5291-5980)
- Wenduo Gu (ORCID: https://orcid.org/0000-0002-3859-3150)
- D. Li (ORCID: https://orcid.org/0000-0003-1015-6298)
- Rohan Shad (ORCID: https://orcid.org/0000-0002-0453-9041)
- Robert Wirka (ORCID: https://orcid.org/0000-0001-9131-9508)
- Chad S. Weldy (ORCID: https://orcid.org/0000-0003-4652-6422)
- Anshul Kundaje (ORCID: https://orcid.org/0000-0003-3084-2287)
- Alex R. Dalal (ORCID: https://orcid.org/0000-0002-9993-3817)
- Paul P. Cheng (ORCID: https://orcid.org/0000-0003-3429-2702)
- Lasemahang Limbu
- Alexa Berezwitz
- William Jackson
- Meghana Iyer
Institutions
- University of North Carolina at Chapel Hill (US)
- Cardiovascular Institute of the South (US)
- Stanford Medicine (US)
- Stanford University (US)
Publication Details
- Journal
- Cell Genomics
- Published
- 2025-10-15
- DOI
- https://doi.org/10.1016/j.xgen.2025.101034
- Citations
- 4
- Primary Topic
- Atherosclerosis and Cardiovascular Diseases
- Type
- article
- Field-Weighted Citation Impact
- 3.19