The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis.
The venous system has been historically understudied despite its critical roles in blood distribution, heart function, and systemic immunity. This study dissects the microanatomy of upper arm veins at the single cell level, and how it relates to wall structure, remodeling processes, and inflammatory...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0296264 |
| _version_ | 1797315895526162432 |
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| author | Miguel G Rojas Zachary M Zigmond Simone Pereira-Simon Nieves Santos Falcon Maya Suresh Kumar Filipe F Stoyell-Conti Christina Kosanovic Anthony J Griswold Alghidak Salama Xiaofeng Yang Marwan Tabbara Roberto I Vazquez-Padron Laisel Martinez |
| author_facet | Miguel G Rojas Zachary M Zigmond Simone Pereira-Simon Nieves Santos Falcon Maya Suresh Kumar Filipe F Stoyell-Conti Christina Kosanovic Anthony J Griswold Alghidak Salama Xiaofeng Yang Marwan Tabbara Roberto I Vazquez-Padron Laisel Martinez |
| author_sort | Miguel G Rojas |
| collection | DOAJ |
| description | The venous system has been historically understudied despite its critical roles in blood distribution, heart function, and systemic immunity. This study dissects the microanatomy of upper arm veins at the single cell level, and how it relates to wall structure, remodeling processes, and inflammatory responses to injury. We applied single-cell RNA sequencing to 4 non-diseased human veins (3 basilic, 1 cephalic) obtained from organ donors, followed by bioinformatic and histological analyses. Unsupervised clustering of 20,006 cells revealed a complex ecosystem of endothelial cell (EC) types, smooth muscle cell (SMCs) and pericytes, various types of fibroblasts, and immune cell populations. The venous endothelium showed significant upregulation of cell adhesion genes, with arteriovenous zonation EC phenotypes highlighting the heterogeneity of vasa vasorum (VV) microvessels. Venous SMCs had atypical contractile phenotypes and showed widespread localization in the intima and media. MYH11+DESlo SMCs were transcriptionally associated with negative regulation of contraction and pro-inflammatory gene expression. MYH11+DEShi SMCs showed significant upregulation of extracellular matrix genes and pro-migratory mediators. Venous fibroblasts ranging from secretory to myofibroblastic phenotypes were 4X more abundant than SMCs and widely distributed throughout the wall. Fibroblast-derived angiopoietin-like factors were identified as versatile signaling hubs to regulate angiogenesis and SMC proliferation. An abundant monocyte/macrophage population was detected and confirmed by histology, including pro-inflammatory and homeostatic phenotypes, with cell counts positively correlated with age. Ligand-receptor interactome networks identified the venous endothelium in the main lumen and the VV as a niche for monocyte recruitment and infiltration. This study underscores the transcriptional uniqueness of venous cells and their relevance for vascular inflammation and remodeling processes. Findings from this study may be relevant for molecular investigations of upper arm veins used for vascular access creation, where single-cell analyses of cell composition and phenotypes are currently lacking. |
| first_indexed | 2024-03-08T03:10:28Z |
| format | Article |
| id | doaj.art-0e219662047b4d7e9027363508a78820 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-08T03:10:28Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0e219662047b4d7e9027363508a788202024-02-13T05:34:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01191e029626410.1371/journal.pone.0296264The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis.Miguel G RojasZachary M ZigmondSimone Pereira-SimonNieves Santos FalconMaya Suresh KumarFilipe F Stoyell-ContiChristina KosanovicAnthony J GriswoldAlghidak SalamaXiaofeng YangMarwan TabbaraRoberto I Vazquez-PadronLaisel MartinezThe venous system has been historically understudied despite its critical roles in blood distribution, heart function, and systemic immunity. This study dissects the microanatomy of upper arm veins at the single cell level, and how it relates to wall structure, remodeling processes, and inflammatory responses to injury. We applied single-cell RNA sequencing to 4 non-diseased human veins (3 basilic, 1 cephalic) obtained from organ donors, followed by bioinformatic and histological analyses. Unsupervised clustering of 20,006 cells revealed a complex ecosystem of endothelial cell (EC) types, smooth muscle cell (SMCs) and pericytes, various types of fibroblasts, and immune cell populations. The venous endothelium showed significant upregulation of cell adhesion genes, with arteriovenous zonation EC phenotypes highlighting the heterogeneity of vasa vasorum (VV) microvessels. Venous SMCs had atypical contractile phenotypes and showed widespread localization in the intima and media. MYH11+DESlo SMCs were transcriptionally associated with negative regulation of contraction and pro-inflammatory gene expression. MYH11+DEShi SMCs showed significant upregulation of extracellular matrix genes and pro-migratory mediators. Venous fibroblasts ranging from secretory to myofibroblastic phenotypes were 4X more abundant than SMCs and widely distributed throughout the wall. Fibroblast-derived angiopoietin-like factors were identified as versatile signaling hubs to regulate angiogenesis and SMC proliferation. An abundant monocyte/macrophage population was detected and confirmed by histology, including pro-inflammatory and homeostatic phenotypes, with cell counts positively correlated with age. Ligand-receptor interactome networks identified the venous endothelium in the main lumen and the VV as a niche for monocyte recruitment and infiltration. This study underscores the transcriptional uniqueness of venous cells and their relevance for vascular inflammation and remodeling processes. Findings from this study may be relevant for molecular investigations of upper arm veins used for vascular access creation, where single-cell analyses of cell composition and phenotypes are currently lacking.https://doi.org/10.1371/journal.pone.0296264 |
| spellingShingle | Miguel G Rojas Zachary M Zigmond Simone Pereira-Simon Nieves Santos Falcon Maya Suresh Kumar Filipe F Stoyell-Conti Christina Kosanovic Anthony J Griswold Alghidak Salama Xiaofeng Yang Marwan Tabbara Roberto I Vazquez-Padron Laisel Martinez The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis. PLoS ONE |
| title | The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis. |
| title_full | The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis. |
| title_fullStr | The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis. |
| title_full_unstemmed | The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis. |
| title_short | The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis. |
| title_sort | intricate cellular ecosystem of human peripheral veins as revealed by single cell transcriptomic analysis |
| url | https://doi.org/10.1371/journal.pone.0296264 |
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