Details for: CL0002139

Cell ID: CL0002139

Cell Name: endothelial cell of vascular tree

Description: These cells are reportedly CD31-positive, CD34-positive, CD144-positive, TAL1-positive.

Synonyms: cubodial endothelial cell of vascular tree, vascular endothelial cell

Selected Context(s): Overall

Gene Significance Landscape

Display Options
Score:
Display
Genes

Contexts:

Cell Significance Index (CSI) is uniquely calculated to reveal cell-specific gene markers. More info here

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for endothelial cell of vascular tree within the selected context(s).

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for endothelial cell of vascular tree. Higher scores indicate a stronger, more significant difference in expression.
(Previously described as "Fold Change", but now represents Cliff's Delta × –log10(p).)

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for endothelial cell of vascular tree. Higher scores indicate a stronger, more significant difference in expression.
Average CSI: csi sum / gene count
Cell network configuration

This network visualizes key genes for endothelial cell of vascular tree. It primarily includes:
1. Top genes highly significant for this cell (Num. Top Cell Genes - based on the 'Min. CSI' setting).
2. Any additional specific 'Context Genes' you add below.
The final network is a combined view. Choose an Interaction Source (pathways or protein interactions) and optionally compare CSI scores with a Baseline Cell Type.

Maximum number of selected genes.
Select a context for the baseline cell.
Select a context for the target cell.
Target Cell for CSI:  endothelial cell of vascular tree (CL0002139)

 Legend
Nodes (Genes):
 Query Gene
Node size also reflects Target Cell CSI magnitude.
Node Color (Target Cell CSI in specific network):
 Very High
 High
 Medium
 Low
 Very Low
 N/A or Not Sig.
Edges (Interactions):
 STRING (Protein-Protein)
 ONTOLOGY (Shared Pathway)
 Colors vary by pathway category; default arrow applies.

Loading network (please wait)...

## Summary The [endothelial cell of the vascular tree](/details-cell/CL0002139) is a specialized cell type forming the inner lining of blood vessels, consistent with its known expression of markers such as CD31, CD34, and CD144. **Overall**, its gene significance profile underscores its fundamental roles in maintaining vascular integrity, regulating hemostasis, and interfacing with the immune system. Key specific markers include genes involved in cell adhesion such as [PCDHB15](/details-gene/56121), and coagulation, like [F12](/details-gene/2161). Intriguingly, the most defining markers by expression specificity include [PRND](/details-gene/23627), a prion-like protein, and [STRC](/details-gene/161497), a protein primarily associated with inner ear function, suggesting novel and underappreciated roles for this cell type beyond its classical functions. ## Key Characteristics and Function The molecular signature of the [endothelial cell of the vascular tree](/details-cell/CL0002139) points to a multifunctional cell critical for vascular homeostasis. Analysis of its top specific markers reveals several core functional clusters. * **Vascular Integrity and Cell Adhesion:** A primary role in forming a cohesive barrier is strongly suggested by the high specificity of various adhesion molecules. These include protocadherin beta 15 ([PCDHB15](/details-gene/56121)), which is part of a family of neural cadherin-like genes ([Link](https://doi.org/10.1016/s0092-8674(00)80789-8)), and [CDH19](/details-gene/913). The high significance of [STRC](/details-gene/161497), a gene involved in cell-matrix adhesion, further supports this role, although its primary association with the inner ear makes its specificity in endothelium a novel observation ([Link](https://doi.org/10.1038/ng726)). * **Immune System Interface:** Endothelial cells serve as a crucial interface between blood and tissue, a role highlighted by the specific expression of immune-related genes. The high significance of Beta-2-microglobulin ([B2M](/details-gene/567)) and the non-classical MHC class Ib molecule [HLA-E](/details-gene/3133) indicates an active role in antigen presentation and immune modulation, likely regulating the activity of circulating immune cells such as T cells and NK cells. * **Hemostasis and Coagulation:** The specific expression of Coagulation Factor XII ([F12](/details-gene/2161)), a key protein in the intrinsic pathway of blood coagulation, directly links this cell type to the regulation of thrombosis and hemostasis, a canonical function of the vascular endothelium. * **Metabolic Specialization:** The anti-marker profile is strikingly dominated by genes essential for mitochondrial oxidative phosphorylation. Numerous mitochondrially-encoded genes, including those for NADH dehydrogenase ([ND1](/details-gene/4535), [ND2](/details-gene/4536), [ND3](/details-gene/4537), [ND4](/details-gene/4538), [ND5](/details-gene/4540)), cytochrome c oxidase ([COX1](/details-gene/4512), [COX2](/details-gene/4513), [COX3](/details-gene/4514)), ATP synthase ([ATP6](/details-gene/4508)), and cytochrome b ([CYTB](/details-gene/4519)), are among the most significantly downregulated genes. This pattern strongly suggests that, relative to other cell types, vascular endothelial cells rely less on mitochondrial respiration and may favor glycolysis to meet their energetic demands, a feature that would preserve oxygen for transport to peripheral tissues. The strong negative signal for T-cell receptor genes like [TRAV39](/details-gene/28642) confirms its distinct, non-lymphoid lineage. ## Clinical Significance and Contextual Roles The gene expression profile of vascular endothelial cells provides insight into their potential roles in various physiological and pathological states. The specific expression of [F12](/details-gene/2161) underscores the endothelium's central role in thrombotic disorders. Dysregulation of endothelial [HLA-E](/details-gene/3133) and [B2M](/details-gene/567) expression may contribute to vascular inflammation, the pathogenesis of atherosclerosis, and immune-mediated rejection of vascularized allografts. The high specificity of several unexpected genes suggests novel clinical connections. The top marker, [PRND](/details-gene/23627), encodes a protein structurally related to the prion protein, and its upregulation in the CNS of PrP-deficient mice has been associated with ataxia and neurodegeneration ([Link](https://pubmed.ncbi.nlm.nih.gov/10525406/)). Its highly specific expression in endothelial cells could implicate the vasculature in prion disease pathogenesis, potentially related to transport across the blood-brain barrier or systemic vascular pathology. Similarly, [STRC](/details-gene/161497) mutations are known to cause non-syndromic deafness and male infertility ([Link](https://doi.org/10.1136/jmg.2006.045765)). Its prominent role as an endothelial marker may indicate an uncharacterized vascular component to these syndromes or a broader function for stereocilin in maintaining structural integrity in tissues beyond the inner ear. The specific expression of the long non-coding RNA [NEAT1](/details-gene/283131), a critical component of nuclear paraspeckles, further points to a complex layer of transcriptional and post-transcriptional regulation unique to these cells, which could be disrupted in vascular diseases. ## Potential Mechanisms and Research Directions 1. **Hypothesis: Vascular endothelial cells express a unique repertoire of "neuro-sensory" adhesion proteins that are critical for specialized barrier functions and cell-cell communication.** The high specificity of genes like [PRND](/details-gene/23627), [STRC](/details-gene/161497), and [PCDHB15](/details-gene/56121), which are traditionally associated with the nervous system and sensory organs, suggests they perform essential, non-canonical roles in the vasculature, possibly mediating interactions at the neurovascular unit or maintaining the integrity of the blood-brain barrier. * **Surprising Findings:** The most specific protein-coding markers for a ubiquitous cell type like vascular endothelium are not classic pan-endothelial genes but rather proteins linked to specific and rare pathologies like prion-related neurodegeneration ([PRND](/details-gene/23627)) and syndromic deafness ([STRC](/details-gene/161497)). This suggests that the unique identity of this cell type is defined by a highly specialized molecular toolkit. * **Testable Questions:** Does the targeted knockout or knockdown of [PRND](/details-gene/23627) or [STRC](/details-gene/161497) in an *in vitro* co-culture model of the blood-brain barrier alter its permeability or affect the survival and function of adjacent astrocytes or neurons? 2. **Hypothesis: The distinct identity of vascular endothelial cells is defined by a profound metabolic shift away from oxidative phosphorylation, a state that is actively maintained to support oxygen transport and endothelial function.** The overwhelming number of mitochondrial respiratory chain components in the anti-marker list suggests that a low rate of oxidative phosphorylation is not merely a passive feature but a defining characteristic of this cell type's specialization. This glycolytic preference likely supports rapid ATP production for dynamic processes like angiogenesis and preserves local oxygen tension for delivery to surrounding tissues. * **Surprising Findings:** It is not just that mitochondrial genes are not top markers, but that they constitute the most significantly repressed gene signature for this cell. This implies that the down-regulation of mitochondrial respiration is a cornerstone of the endothelial cell's functional identity, more so than for many other cell types. * **Testable Questions:** Using metabolic flux analysis (e.g., Seahorse assays), do primary vascular endothelial cells exhibit a uniquely high glycolytic rate and low oxygen consumption rate at baseline compared to other stromal cells from the same tissue? Furthermore, does inhibition of key glycolytic enzymes disproportionately affect endothelial cell viability and barrier function compared to inhibition of the electron transport chain?