Details for: CL0001065

Cell ID: CL0001065

Cell Name: innate lymphoid cell

Description: A lymphocyte that lacks characteristic T cell, B cell, myeloid cell, and dendritic cell markers, that functions as part of the innate immune response to produce cytokines and other effector responses.

Selected Context(s): Overall

Gene Significance Landscape

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Score:
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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 innate lymphoid cell 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 innate lymphoid cell. 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 innate lymphoid cell. 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 innate lymphoid cell. 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:  innate lymphoid cell (CL0001065)

 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.

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## Summary The [innate lymphoid cell](/details-cell/CL0001065) (ILC) is a component of the innate immune system, characterized by its lymphocyte morphology but lacking markers of T cells, B cells, or myeloid lineages. Transcriptomic analysis based on expression specificity (**Overall** context) reveals a highly distinct cellular identity. The most defining markers are not classical immune effector molecules, but rather a unique combination of uncharacterized non-coding RNAs, such as [LOC101928940](/details-gene/101928940) and [TMEM123 DT](/details-gene/101928424), alongside a suite of cell adhesion molecules including [STRC](/details-gene/161497) and [PCDHB15](/details-gene/56121). This suggests that the unique identity of ILCs is defined by a specific transcriptional regulatory network and a strong capacity for interaction with their tissue microenvironment. ## Key Characteristics and Function Analysis of top marker genes, ranked by expression specificity (CSI Z-Score), provides insight into the core functional attributes of [innate lymphoid cells](/details-cell/CL0001065). These genes can be grouped into several functional clusters. * **Tissue Interaction and Adhesion:** A prominent feature is the high specificity of multiple cell adhesion genes. These include [STRC](/details-gene/161497), involved in cell-matrix adhesion, as well as protocadherin [PCDHB15](/details-gene/56121) and cadherin [CDH19](/details-gene/28513). The unique expression of these molecules strongly suggests that ILCs are adapted for tissue residency, engaging in specific cell-cell and cell-matrix interactions that are likely critical for their maintenance, localization, and function within diverse anatomical niches. * **Transcriptional and Translational Readiness:** The cell is characterized by high-level expression of genes essential for protein synthesis and stability. This includes the translationally controlled tumor protein [TPT1](/details-gene/7178), the poly(A)-binding protein [PABPC1](/details-gene/26986), translation elongation factor [EEF1B2](/details-gene/1933), and the general transcription factor [BTF3](/details-gene/689). This molecular signature indicates that ILCs are maintained in a state of high metabolic and translational readiness, poised to rapidly execute their effector functions, such as cytokine production, upon activation. * **Core Immune Identity:** The high specificity of Beta-2-microglobulin ([B2M](/details-gene/567)) underscores the cell's lymphoid lineage. As a key component of MHC class I molecules, its expression is consistent with the potential for ILCs to interact with and be regulated by cytotoxic cells of the adaptive immune system, such as CD8+ T cells. * **Iron Metabolism:** A notable characteristic is the specific expression of both ferritin light chain ([FTL](/details-gene/2512)) and heavy chain ([FTH1](/details-gene/2495)). This points towards a specialized role in iron sequestration and management, a process crucial for both cellular metabolism and antimicrobial defense through iron withholding. * **Unique Regulatory Network:** The most specific markers for ILCs are several uncharacterized non-coding RNAs, including [LOC101928940](/details-gene/101928940), [TMEM123 DT](/details-gene/101928424), and [LINC02877](/details-gene/152118). This finding suggests that a significant layer of cell-type-specific regulation, mediated by lncRNAs, is fundamental to establishing and maintaining the ILC phenotype. The anti-marker profile further refines this identity. The significantly low expression specificity of genes like the cytokine [IL31](/details-gene/386653) and various long non-coding RNAs (e.g., [CACNA1G AS1](/details-gene/253962), [TBC1D8 AS1](/details-gene/100506286)) confirms that the ILC transcriptional program is highly specialized and distinct from other immune and non-immune cell types. ## Clinical Significance and Contextual Roles Although this analysis reflects an **Overall** state without a direct disease comparison, the functions of several top marker genes suggest potential roles for ILCs in specific pathologies. The high specificity of [STRC](/details-gene/161497) is particularly intriguing. Mutations in [STRC](/details-gene/161497) are a known cause of non-syndromic deafness ([Link](https://doi.org/10.1038/ng726)) and are implicated in a contiguous gene deletion syndrome causing both deafness and male infertility ([Link](https://doi.org/10.1136/jmg.2006.045765)). While [STRC](/details-gene/161497) function is primarily studied in inner ear hair cells, its highly specific expression in ILCs may suggest a previously unappreciated role for these immune cells in the pathology of the inner ear, potentially related to inflammation or tissue homeostasis. Furthermore, the prion-like protein doppel, encoded by [PRND](/details-gene/23627), is another top marker. Upregulation of [PRND](/details-gene/23627) has been associated with ataxia and neurodegeneration in prion protein-deficient mice ([Link](https://doi.org/10.1006/jmbi.1999.3108)). The specific expression of this gene by ILCs could implicate these cells in the immune surveillance of the central nervous system or suggest their potential involvement in the progression of certain neurodegenerative disorders. Collectively, the unique gene signature of ILCs, especially the expression of tissue-specific pathology-associated genes, hints at highly specialized, context-dependent roles in health and disease that extend beyond their canonical function as innate cytokine producers. ## Potential Mechanisms and Research Directions Based on the gene significance profiles, several hypotheses regarding ILC biology can be formulated. 1. **Hypothesis:** The identity and function of ILCs are critically dependent on their physical anchoring and communication within specific tissue microenvironments, mediated by a unique repertoire of cell adhesion molecules. * **Surprising Findings:** The most specific adhesion molecule identified, [STRC](/details-gene/161497), is almost exclusively studied in the context of inner ear stereocilia structure. Its status as a top ILC marker is highly unexpected and suggests a novel, shared molecular mechanism for cell-matrix interaction between specialized sensory epithelia and innate lymphocytes. * **Testable Questions:** Does the conditional deletion of [STRC](/details-gene/161497) in hematopoietic cells impact the development, tissue localization, or retention of ILCs in mucosal barriers or other tissues? Do ILCs co-localize with [STRC](/details-gene/161497)-associated matrix proteins *in situ*? 2. **Hypothesis:** A cell-type-specific network of long non-coding RNAs (lncRNAs) acts as a primary regulatory layer that establishes and maintains the unique transcriptional identity of ILCs, controlling their state of readiness and poised effector functions. * **Surprising Findings:** The genes with the highest expression specificity (e.g., [LOC101928940](/details-gene/101928940), [TMEM123 DT](/details-gene/101928424)) are not well-characterized protein-coding genes but unannotated lncRNAs. This implies that what most distinguishes ILCs from other cells is their regulatory architecture, rather than the effector molecules themselves. * **Testable Questions:** What are the protein and/or RNA interaction partners of the lncRNA [LOC101928940](/details-gene/101928940) in primary human ILCs? Does CRISPR-interference-mediated knockdown of this lncRNA alter the baseline expression of key ILC transcription factors (e.g., RORγt, T-bet) or impair their ability to produce cytokines upon stimulation?