Single-cell RNA-seq of the mouse and human lymph node lymphatic vasculature
Abstract/Contents
- Abstract
- Single-cell transcriptomics promises to revolutionize our understanding of the vasculature. Emerging computational methods applied to high dimensional single cell data allow integration of results between samples and species, and illuminate the diversity and underlying developmental and architectural organization of cell populations. Here, we illustrate these methods in analysis of mouse lymph node (LN) lymphatic endothelial cells (LEC) at single cell resolution. Clustering identifies five well-delineated subsets, including two medullary sinus subsets not recognized previously as distinct. Nearest neighbor alignments in trajectory space position the major subsets in a sequence that recapitulates known and suggests novel features of LN lymphatic organization, providing a transcriptional map of the lymphatic endothelial niches and of the transitions between them. Differences in gene expression reveal specialized programs for (1) subcapsular ceiling endothelial interactions with the capsule connective tissue and cells, (2) subcapsular floor regulation of lymph borne cell entry into the LN parenchyma and antigen presentation, and (3) medullary subset specialization for pathogen interactions and LN remodeling. LEC of the subcapsular sinus floor and medulla, which represent major sites of cell entry and exit from the LN parenchyma respectively, respond robustly to oxazolone inflammation challenge with enriched signaling pathways that converge on both innate and adaptive immune responses. Integration of mouse and human single-cell profiles reveals a conserved cross-species pattern of lymphatic vascular niches and gene expression, as well as specialized human subsets and genes unique to each species. The examples provided demonstrate the power of single-cell analysis in elucidating endothelial cell heterogeneity, vascular organization and endothelial cell responses. We discuss the findings from the perspective of LEC functions in relation to niche formations in the unique stromal and highly immunological environment of the LN.
Description
| Type of resource | software, multimedia |
|---|---|
| Date created | January 2020 |
Creators/Contributors
| Author | Xiang, Menglan |
|---|
Subjects
| Subject | lymph node |
|---|---|
| Subject | lymphatic endothelial cells |
| Subject | single-cell RNA sequencing |
| Subject | trajectory inference |
| Subject | cross-species mapping |
| Subject | endothelial cell heterogeneity |
| Subject | computational vascular modeling |
| Genre | Dataset |
Bibliographic information
| Related Publication | Xiang M, Grosso RA, Takeda A, et al. A Single-Cell Transcriptional Roadmap of the Mouse and Human Lymph Node Lymphatic Vasculature. Front Cardiovasc Med. 2020;7:52. Published 2020 Apr 30. doi:10.3389/fcvm.2020.00052 |
|---|---|
| Related item | |
| Location | https://purl.stanford.edu/xr811qy1057 |
Access conditions
- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
Preferred citation
- Preferred Citation
- Single-cell RNA-seq of the mouse and human lymph node lymphatic vasculature https://purl.stanford.edu/xr811qy1057
Collection
Stanford Research Data
View other items in this collection in SearchWorksContact information
- Contact
- mxiang1@stanford.edu
Also listed in
Loading usage metrics...