Details for: CL0002138

Cell ID: CL0002138

Cell Name: endothelial cell of lymphatic vessel

Description: A endothelial cell of a lymphatic vessel. The border of the oak leaf-shaped endothelial cell of initial lymphatics are joined by specialized buttons. The discontinuous feature of buttons distinguishes them from zippers in collecting lymphatics, but both types of junctions are composed of proteins typical of adherens junctions and tight junctions found in the endothelium of blood vessels. Buttons seal the sides of flaps of the oak leaf-shaped endothelial cell, leaving open the tips of flaps as routes for fluid entry without disassembly and reformation of intercellular junctions.

Synonyms: LEC, lymphatic endothelial cell

Selected Context(s): Overall

Gene Significance Landscape

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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 lymphatic vessel 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 lymphatic vessel. 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 lymphatic vessel. 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 lymphatic vessel. 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.

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Select a context for the target cell.
Target Cell for CSI:  endothelial cell of lymphatic vessel (CL0002138)

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

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## Summary The [endothelial cell of lymphatic vessel](/details-cell/CL0002138) (LEC) is a specialized endothelial cell type that forms the lining of lymphatic capillaries and collecting vessels. Structurally, these cells are characterized by discontinuous "button-like" intercellular junctions that facilitate the entry of interstitial fluid, macromolecules, and immune cells into the lymphatic system. Based on its gene significance profile, this cell type is not merely a passive conduit but also plays a substantial role in immune surveillance. The high expression specificity of genes involved in antigen presentation, particularly the non-classical MHC class I molecule [HLA E](/details-gene/3133) and its partner [B2M](/details-gene/567), suggests that LECs are active participants in modulating immune responses at the interface between peripheral tissues and the draining lymph nodes. ## Key Characteristics and Function **Overall**, the gene expression profile of the [endothelial cell of lymphatic vessel](/details-cell/CL0002138) points to a cell that is both structurally specialized and immunologically active, with a high basal metabolic rate to support these functions. The top markers can be grouped into several key functional clusters. * **Immune Surveillance and Antigen Presentation:** The most striking feature is the high significance of genes associated with the MHC class I pathway. The non-classical class I molecule [HLA E](/details-gene/3133) (CSI: 37.50) and its essential light chain component Beta-2-microglobulin ([B2M](/details-gene/567); CSI: 35.08) are the top two markers. This strongly suggests that LECs are capable of antigen presentation. Unlike classical HLA-A, B, and C molecules that primarily present peptides to cytotoxic [T-lymphocytes](/details-cell/CL0000084), [HLA E](/details-gene/3133) is known to present a restricted set of peptides and primarily interacts with inhibitory receptors (like NKG2A/CD94) on Natural Killer (NK) cells and subsets of T cells ([Link](https://pubmed.ncbi.nlm.nih.gov/3260916/)). This implies a specialized role for LECs in regulating innate and adaptive immune cell activation at the gateway to the lymphatic system. * **High Metabolic and Biosynthetic Activity:** A large number of the top markers are involved in fundamental cellular processes, and their high specificity scores suggest these pathways are exceptionally active in LECs. This includes genes for protein translation ([TPT1](/details-gene/7178), [PABPC1](/details-gene/26986), [EEF1D](/details-gene/1936)), protein folding and processing ([UBC](/details-gene/7316), [DDX5](/details-gene/1655)), and energy production ([ATP5F1E](/details-gene/514), [SLC25A6](/details-gene/293), [COX4I1](/details-gene/2114)). The high significance of Ferritin Light Chain ([FTL](/details-gene/2512); CSI: 31.30) also points to a critical role for iron metabolism and storage, likely supporting the high energetic demands of the cell. * **Cytoskeletal Dynamics and Cell Adhesion:** Genes related to the cytoskeleton, such as myosin light chains ([MYL6](/details-gene/4637), [MYL12B](/details-gene/103910)) and the actin-depolymerizing factor cofilin 1 ([CFL1](/details-gene/2283)), show significant expression specificity. This is consistent with the cell's role in maintaining the structural integrity of the lymphatic vessel, regulating endothelial permeability through its button-like junctions, and responding to mechanical cues like fluid shear stress. * **Amyloid Precursor Processing:** A notable top marker is Integral Membrane Protein 2B ([ITM2B](/details-gene/9445); CSI: 29.48), mutations in which are linked to familial British and Danish dementias through the generation of amyloidogenic peptides ([Link](https://doi.org/10.1038/21637)). Its specific expression in LECs may indicate a role for the lymphatic system in the clearance of amyloid-like proteins from tissues. The **Anti_Markers** profile helps to refine the cell's identity. The lack of significant expression for genes like the proto-oncogene [MYCN](/details-gene/4613), the developmental transcription factor [MSX1](/details-gene/4487), and the hematopoietic cytokine [CSF2](/details-gene/1437) (GM-CSF) confirms that this is a mature, differentiated endothelial cell type, distinct from progenitor, neuronal, or hematopoietic lineages. ## Clinical Significance and Contextual Roles Although this analysis is based on an **Overall** context, the gene signature of LECs has profound implications for various physiological and pathological processes. The prominent expression of [HLA E](/details-gene/3133) and [B2M](/details-gene/567) positions LECs as critical gatekeepers of the immune response. In cancer, tumor-draining lymphatic vessels are a primary route for metastasis. The ability of LECs to present tumor-derived antigens could either promote anti-tumor immunity by activating T cells or, conversely, induce tolerance, thereby facilitating tumor escape. Similarly, during viral or bacterial infections, LECs may present microbial antigens to draining lymph nodes, shaping the ensuing adaptive immune response. The high expression of [ITM2B](/details-gene/9445) is particularly intriguing. This gene is primarily associated with rare, inherited forms of dementia characterized by cerebral amyloid angiopathy ([Link](https://doi.org/10.1073/pnas.080076097)). Its significance in LECs suggests a potential, previously underappreciated role for the peripheral lymphatic system in systemic proteostasis and the clearance of amyloidogenic proteins. Dysfunction in lymphatic drainage is increasingly linked to diseases involving protein aggregation, including neurodegenerative disorders where brain clearance pathways connect to cervical lymphatics. Furthermore, several top markers like the calcium-binding protein [S100A6](/details-gene/6277) and the long non-coding RNA [NEAT1](/details-gene/283131) are implicated in inflammatory processes and cancer progression. Their specific expression in LECs could be relevant to pathologies involving lymphangiogenesis (the formation of new lymphatic vessels), which is a hallmark of chronic inflammation and tumor growth. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** Lymphatic endothelial cells act as specialized regulators of innate immunity at the tissue-lymph node interface, primarily through the presentation of self-peptides via the non-classical MHC molecule [HLA E](/details-gene/3133) to inhibit NK cell-mediated cytotoxicity and maintain peripheral tolerance. * **Surprising Findings:** The dominance of a non-classical, primarily inhibitory MHC molecule ([HLA E](/details-gene/3133)) over classical MHC-I molecules as a top defining marker is unexpected. This suggests that the default function of LECs may be to actively suppress, rather than activate, certain arms of the immune system, possibly to prevent inappropriate inflammation in response to the constant flow of antigens from the periphery. * **Testable Questions:** Does the specific knockdown of [HLA E](/details-gene/3133) in an *in vitro* co-culture model of LECs and primary human NK cells lead to increased LEC lysis and NK cell degranulation? Can this effect be modulated by loading LECs with specific HLA-E-binding peptides? 2. **Hypothesis:** Lymphatic endothelial cells contribute to systemic proteostasis by actively participating in the binding and transport of amyloidogenic proteins, a process mediated in part by molecules such as [ITM2B](/details-gene/9445). Dysfunction of this LEC-mediated clearance mechanism could contribute to the pathogenesis of diseases characterized by protein aggregation. * **Surprising Findings:** The identification of a gene ([ITM2B](/details-gene/9445)) directly linked to familial dementias as a highly specific marker for a peripheral endothelial cell is a novel finding. It challenges the brain-centric view of these pathologies and suggests a systemic component involving lymphatic clearance that could be a potential therapeutic target. * **Testable Questions:** Using a mouse model, can fluorescently-tagged amyloid-beta or ABri peptides be observed binding to and being internalized by lymphatic vessels in peripheral tissues (e.g., skin) following interstitial injection? Does genetic ablation of *Itm2b* in mouse LECs impair the clearance of these peptides to the draining lymph node?