Details for: CL0002376

Cell ID: CL0002376

Cell Name: non-myelinating Schwann cell

Description: A glial cell that ensheaths multiple small diameter axons in the peripheral nervous system. The non-myelinating Schwann cell is embedded among neurons (axons) with minimal extracellular spaces separating them from nerve cell membranes and has a basal lamina. Cells can survive without an axon present. These cells can de-differentiate into immature Schwann cells.

Synonyms: Schwann 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 non-myelinating Schwann 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 non-myelinating Schwann 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 non-myelinating Schwann 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 non-myelinating Schwann 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.
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Select a context for the target cell.
Target Cell for CSI:  non-myelinating Schwann cell (CL0002376)

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Nodes (Genes):
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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 [non-myelinating Schwann cell](/details-cell/CL0002376), also known as a Remak cell, is a glial cell type in the peripheral nervous system responsible for ensheathing multiple small-diameter axons. The provided gene significance profile highlights its fundamental role in neuronal interaction, cytoskeletal organization, and signaling. **Overall**, the top marker genes based on expression specificity (Z-score CSI) such as the glycoprotein [GPM6B](/details-gene/2824), the transcription factor [ZBTB20](/details-gene/26137), and the cell adhesion molecule [CHL1](/details-gene/10752), underscore a complex cellular program dedicated to maintaining axonal integrity, regulating local signaling, and contributing to the structural framework of peripheral nerves. ## Key Characteristics and Function The functional identity of the [non-myelinating Schwann cell](/details-cell/CL0002376) is defined by several clusters of specifically expressed genes. * **Axonal Adhesion and Communication:** A prominent functional signature is the expression of numerous genes involved in cell-cell interaction, particularly with neurons. Top markers include [CHL1](/details-gene/10752), a member of the L1 family of neural cell adhesion molecules, and the neurexins [NRXN1](/details-gene/9378) and [NRXN3](/details-gene/9369), which are critical for synaptic organization and signaling. Additionally, the expression of [CADM1](/details-gene/23705) and [CADM2](/details-gene/253559) suggests a role in homophilic adhesion that may be essential for bundling and segregating axons within Remak bundles. The specific expression of [SCN7A](/details-gene/6332), a voltage-gated sodium channel, may also indicate a role in modulating axonal excitability. * **Membrane and Cytoskeletal Dynamics:** The cell's unique morphology, which involves extending thin cytoplasmic processes to envelop multiple axons, is supported by specific expression of cytoskeletal and membrane-associated proteins. [DST](/details-gene/667), an actin and microtubule cross-linking factor, and [SPTBN1](/details-gene/6711) (beta-spectrin) are likely crucial for structural integrity. [PMP22](/details-gene/5376), while famous for its role in compact myelin, is a defining marker here, suggesting a broader function in peripheral nerve membrane biology beyond myelination. The phospholipid scramblase [XKR4](/details-gene/114786) may be involved in membrane maintenance and signaling. * **Transcriptional and Post-transcriptional Regulation:** The cell's phenotype appears to be maintained by specific transcriptional repressors, including [ZBTB20](/details-gene/26137) and [ZEB2](/details-gene/9839). The high specificity of the long non-coding RNA [NEAT1](/details-gene/283131), a key component of nuclear paraspeckles, points towards a significant role for nuclear architecture and post-transcriptional control in regulating the cell's specialized functions. * **Immune and Stress Response:** [Non-myelinating Schwann cells](/details-cell/CL0002376) express a suite of genes suggesting a role in immune surveillance within the peripheral nerve. The expression of [B2M](/details-gene/567), a component of MHC class I molecules, implies a capacity for antigen presentation. This is further supported by markers like [SAMHD1](/details-gene/25939) and the interferon-inducible gene [IFITM3](/details-gene/10410), which are involved in innate antiviral responses. * **Lack of Myelin-Program Specialization:** While sharing some markers with their myelinating counterparts (e.g., [PMP22](/details-gene/5376)), the anti-marker profile, though not strongly negative, indicates a lack of enrichment for genes associated with other lineages. The low scores for RNA binding proteins like [DDX5](/details-gene/1655) and [RBM39](/details-gene/9584) may reflect a distinct post-transcriptional regulatory network compared to other cell types. ## Clinical Significance and Contextual Roles The gene expression profile of [non-myelinating Schwann cells](/details-cell/CL0002376) provides a direct link to several human diseases, primarily peripheral neuropathies and neurodevelopmental disorders. The high specificity of [PMP22](/details-gene/5376) is clinically significant, as mutations in this gene are a primary cause of Charcot-Marie-Tooth disease type 1A, a common inherited peripheral neuropathy ([Link](https://doi.org/10.1038/ng0692-159)). This suggests that even in a non-myelinating context, proper [PMP22](/details-gene/5376) function is critical for nerve health. Similarly, mutations in [DST](/details-gene/667) are associated with hereditary sensory and autonomic neuropathy. Several top markers are implicated in neurodevelopmental and neurodegenerative conditions. For instance, [IL1RAPL1](/details-gene/11141) is involved in a form of X-linked mental retardation ([Link](https://doi.org/10.1038/12623)), and deletions involving [NRXN1](/details-gene/9378) have been associated with autism spectrum disorder ([Link](https://doi.org/10.1016/j.ajhg.2007.09.011)). The amyloid precursor protein, [APP](/details-gene/351), a central molecule in Alzheimer's disease, is also a specific marker, suggesting a potential role for these cells in amyloid processing or response in the peripheral nervous system. The transcription factor [ZEB2](/details-gene/9839) is mutated in Mowat-Wilson syndrome, which includes Hirschsprung disease as a feature, highlighting the gene's critical role in neural crest-derived cell development. Collectively, this evidence places the [non-myelinating Schwann cell](/details-cell/CL0002376) at the intersection of nerve maintenance, development, and pathology. Dysregulation of its core functions in axonal adhesion, cytoskeletal stability, or local signaling likely contributes significantly to the pathophysiology of various peripheral nerve disorders. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** [Non-myelinating Schwann cells](/details-cell/CL0002376) function as local immune sentinels within peripheral nerves, capable of detecting pathogens and injury and initiating an immune response through antigen presentation. * **Surprising Findings:** The co-expression of multiple interferon-inducible genes ([SAMHD1](/details-gene/25939), [IFITM3](/details-gene/10410)) alongside a core component of the MHC class I antigen presentation pathway ([B2M](/details-gene/567)) is unexpected for a cell traditionally viewed as purely structural support. This suggests a more proactive role in neuro-immunology than previously appreciated. * **Testable Questions:** Upon exposure to viral ligands (e.g., poly(I:C)) or pro-inflammatory cytokines, do cultured [non-myelinating Schwann cells](/details-cell/CL0002376) upregulate the full antigen processing and presentation machinery, and can they subsequently activate antigen-specific [CD8-positive, alpha-beta T cells](/details-cell/CL0000625) in a co-culture assay? 2. **Hypothesis:** The specific combination of expressed cell adhesion molecules ([CHL1](/details-gene/10752), [CADM1](/details-gene/23705), [NRXN1](/details-gene/9378)) and cytoskeletal linkers ([DST](/details-gene/667)) constitutes a molecular "code" that governs the precise sorting and ensheathment of small-caliber axons, and disruption of this code is a key pathogenic event in peripheral neuropathies. * **Surprising Findings:** The cell expresses a surprisingly diverse and specific repertoire of neuronal interaction molecules, including multiple neurexins ([NRXN1](/details-gene/9378), [NRXN3](/details-gene/9369)) and cadherins ([CADM1](/details-gene/23705), [CADM2](/details-gene/253559)). This complexity suggests a sophisticated mechanism for recognizing and maintaining relationships with distinct axonal subtypes, rather than a generic ensheathment process. * **Testable Questions:** Does selective knockdown of [CHL1](/details-gene/10752) versus [CADM1](/details-gene/23705) in an in vitro Remak bundle formation assay (using co-cultured dorsal root ganglia neurons and Schwann cells) lead to distinct defects in axon bundling, segregation, or long-term maintenance?