Details for: CL0000775

Cell ID: CL0000775

Cell Name: neutrophil

Description: Any of the immature or mature forms of a granular leukocyte that in its mature form has a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.

Synonyms: PMN, neutrocyte, neutrophil leucocyte, neutrophil leukocyte, neutrophilic leucocyte, neutrophilic leukocyte, poly, polymorphonuclear leucocyte, polymorphonuclear leukocyte, polymorphonuclear neutrophil, polynuclear neutrophilic leucocyte, polynuclear neutrophilic leukocyte

Selected Context(s): Overall

Gene Significance Landscape

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Genes

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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 neutrophil 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 neutrophil. 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 neutrophil. 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 neutrophil. 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:  neutrophil (CL0000775)

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Nodes (Genes):
 Query Gene
Node size also reflects Target Cell CSI magnitude.
Node Color (Target Cell CSI in specific network):
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 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 [neutrophil](/details-cell/CL0000775) is a polymorphonuclear granular leukocyte, recognized as a primary effector cell of the innate immune system. The gene significance profile suggests its identity is defined not only by its antimicrobial functions but also by a unique metabolic state and a sophisticated capacity for immune signaling and regulation. High specificity scores for genes involved in MHC class I presentation ([B2M](/details-gene/567)), calcium signaling ([S100A6](/details-gene/6277)), and iron metabolism ([FTL](/details-gene/2512)) highlight a cell equipped for diverse roles beyond simple phagocytosis. Conversely, the strong negative significance of nearly all mitochondrial electron transport chain components underscores a reliance on glycolytic metabolism, a key adaptation for function in hypoxic inflammatory environments. ## Key Characteristics and Function **Overall**, the gene expression landscape of the [neutrophil](/details-cell/CL0000775) portrays a cell in a state of high metabolic and translational readiness, poised for rapid and diverse immune responses. * **Immune Signaling and Antigen Presentation:** The high significance of [B2M](/details-gene/567), the light chain of MHC class I molecules, suggests a potentially underappreciated role for [neutrophils](/details-cell/CL0000775) in presenting endogenous antigens. This is complemented by significant expression of the MHC class II gene [HLA-DPA1](/details-gene/3113), indicating a capacity to engage with the adaptive immune system. Furthermore, high expression of [FCN1](/details-gene/2219), a pattern recognition receptor involved in the lectin complement pathway, and [CD163](/details-gene/9332), a scavenger receptor, solidifies its role as a sentinel and clearance cell. The calcium-binding protein [S100A6](/details-gene/6277) points to the importance of calcium-mediated signaling pathways, likely governing key functions such as chemotaxis, degranulation, and the oxidative burst. * **Metabolic and Biosynthetic Profile:** A defining characteristic is the strong negative significance of a large suite of genes encoding components of the mitochondrial respiratory chain, including [ND1](/details-gene/4535), [ND2](/details-gene/4536), [ND3](/details-gene/4537), [ND4](/details-gene/4538), [COX1](/details-gene/4512), [COX2](/details-gene/4513), [ATP6](/details-gene/4508), and [CYTB](/details-gene/4519). This profile is consistent with a primary reliance on anaerobic glycolysis for ATP production, allowing the cell to function effectively in the low-oxygen environments of inflamed or necrotic tissues. Concurrently, the high significance of genes involved in polyamine metabolism ([SAT1](/details-gene/6303), [OAZ1](/details-gene/4946)) and iron homeostasis ([FTL](/details-gene/2512), [FTH1](/details-gene/2495)) suggests that tight regulation of these pathways is critical for neutrophil function, potentially for controlling cellular proliferation signals and managing oxidative stress or sequestering iron from pathogens. * **Transcriptional and Translational Machinery:** The high CSI (Z-SCORE) values for several ribosomal protein pseudogenes (e.g., [RPL36AP37](/details-gene/729362), [RPL18AP3](/details-gene/390354)) and mitochondrial ribosomal RNAs ([RNR1](/details-gene/4549), [RNR2](/details-gene/4550)) may indicate a unique regulatory landscape or an exceptionally high state of translational readiness. The significance of the long non-coding RNA [NEAT1](/details-gene/283131), a key component of nuclear paraspeckles, further points to complex post-transcriptional gene regulation within these cells. ## Clinical Significance and Contextual Roles The defining genes of [neutrophils](/details-cell/CL0000775) are implicated in a range of clinical contexts, from autoimmunity to cancer, highlighting the cell's broad impact on human health and disease. The high expression of [CD24](/details-gene/100133941) is particularly noteworthy, as a specific polymorphism in this gene has been associated with protection against autoimmune diseases like multiple sclerosis and systemic lupus erythematosus ([Link](https://doi.org/10.1371/journal.pgen.0030049)). This suggests that [neutrophil](/details-cell/CL0000775)-mediated signaling via [CD24](/details-gene/100133941) may be a critical checkpoint in maintaining immune tolerance. The calcium-binding protein [S100A6](/details-gene/6277) has been identified as a growth factor-inducible gene whose mRNA levels are elevated in human acute myeloid leukemia ([Link](https://doi.org/10.1016/s0021-9258(18)67137-6)), pointing to a potential role for this [neutrophil](/details-cell/CL0000775) marker in hematopoietic malignancies. The unique metabolic state, defined by low reliance on oxidative phosphorylation, is clinically relevant as it allows [neutrophils](/details-cell/CL0000775) to be the first responders to, and primary cellular components of, abscesses and other hypoxic sites of infection. The prominent role of iron-sequestering ferritin proteins ([FTL](/details-gene/2512) and [FTH1](/details-gene/2495)) may represent an intrinsic host-defense mechanism known as nutritional immunity, whereby limiting the availability of essential micronutrients like iron inhibits pathogen growth. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The high co-expression of components for both MHC class I ([B2M](/details-gene/567)) and class II ([HLA-DPA1](/details-gene/3113)) presentation machinery indicates that [neutrophils](/details-cell/CL0000775) function as non-professional but contextually important antigen-presenting cells, capable of shaping adaptive T cell responses directly at sites of inflammation. * **Surprising Findings:** The designation of both MHC class I and class II components as defining markers for a cell traditionally considered a short-lived phagocyte with limited antigen presentation capacity is unexpected and challenges its classical role in immunology. * **Testable Questions:** Can [neutrophils](/details-cell/CL0000775) that have phagocytosed bacteria or apoptotic cells effectively process and present peptides via both MHC class I and class II pathways to activate antigen-specific CD8+ and CD4+ T cells, respectively, in a co-culture system? 2. **Hypothesis:** The distinct metabolic signature, marked by profound downregulation of mitochondrial respiratory chain genes and high expression of ferritin subunits ([FTL](/details-gene/2512), [FTH1](/details-gene/2495)), is a key evolutionary adaptation that couples antimicrobial activity with survival in harsh inflammatory microenvironments. * **Surprising Findings:** While reliance on glycolysis is a known feature, the exceptional specificity score for ferritin genes suggests their function in [neutrophils](/details-cell/CL0000775) is a highly specialized, defining characteristic rather than a general housekeeping role, potentially linking iron metabolism directly to effector functions. * **Testable Questions:** Does the functional knockdown of [FTH1](/details-gene/2495) or [FTL](/details-gene/2512) in human [neutrophils](/details-cell/CL0000775) lead to increased intracellular pathogen survival and compromise the cell's ability to form neutrophil extracellular traps (NETs), particularly under hypoxic conditions that mimic an abscess?