Details for: CL0000134

Cell ID: CL0000134

Cell Name: mesenchymal stem cell

Description: Many but not all mesenchymal cells derive from the mesoderm. MSCs are reportedly CD3-negative, CD4-negative, CD5-negative, CD8-negative, CD11a-negative, CD11b-negative, CD14-negative, CD19-negative, CD29-positive, CD31-negative, CD34-negative, CD38-negative, CD40-negative, CD44-positive, CD45-negative, CD49-positive, CD54-positive, CD66b-negative, CD79a-negative, CD80-negative, CD102-positive, CD106-positive, CD117-positive, CD121a-positive, CD121b-positive, CD123-positive, CD124-positive, CD133-negative, CD146-positive, CD166-positive, CD271-positive, B220-negative, Gr1-negative, MHCI-positive, MHCII-negative, SSEA4-negative, sca1-positive, Ter119-negative, and glycophorin A-negative. Cultured MSCs are capable of producing stem cell factor, IL7, IL8, IL11, TGF-beta, cofilin, galectin-1, laminin-receptor 1, cyclophilin A, and MMP-2.

Synonyms: bone marrow stromal cells, colony-forming unit-fibroblast, mesenchymal precursor cell, mesenchymal stem cell, mesenchymal stromal cell, BMSC, CFU-F, MSC, marrow stromal cells, mesenchymal progenitor cells, mesenchymal stromal cells, stem cells, mesenchymal

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 mesenchymal stem 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 mesenchymal stem 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 mesenchymal stem 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 mesenchymal stem 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:  mesenchymal stem cell (CL0000134)

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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 [mesenchymal stem cell](/details-cell/CL0000134) (MSC), also known as a mesenchymal stromal cell, is a multipotent progenitor cell capable of differentiating into various lineages including osteoblasts, chondrocytes, and adipocytes. Based on its gene significance profile, this cell type is characterized by exceptionally high and specific expression of genes involved in fundamental biosynthetic and regulatory processes. The top markers, such as [NPM1](/details-gene/4869) (nucleophosmin), [TPT1](/details-gene/7178) (tumor protein, translationally-controlled 1), and multiple heterogeneous nuclear ribonucleoproteins, underscore a state of high readiness for protein synthesis, RNA processing, and metabolic activity. This profile is consistent with a cell primed for rapid proliferation, self-renewal, and execution of complex differentiation programs in response to tissue-specific cues. ## Key Characteristics and Function The functional identity of the [mesenchymal stem cell](/details-cell/CL0000134) is defined by a distinct set of highly specific gene expression patterns, as indicated by their high `csi_z` scores. These can be grouped into several core biological themes. * **Ribosome Biogenesis and Protein Synthesis:** The most specific marker is [NPM1](/details-gene/4869) (CSI: 7.96), a key regulator of ribosome biogenesis and export. This is complemented by other markers like [NCL](/details-gene/4691) (nucleolin) and [EEF1B2](/details-gene/1933) (eukaryotic translation elongation factor 1 beta 2). This collective signature suggests that a high capacity for protein production is a defining feature of MSCs, likely essential for maintaining their cellular machinery and for rapidly producing lineage-specific proteins upon differentiation. * **RNA Processing and Post-Transcriptional Regulation:** MSCs exhibit specific expression of a suite of RNA-binding proteins, including [HNRNPA1](/details-gene/3178), [HNRNPA2B1](/details-gene/3181), and [PABPC1](/details-gene/26986). These proteins are critical for mRNA splicing, stability, and transport. This indicates the presence of a sophisticated post-transcriptional regulatory network that likely plays a crucial role in managing the switch between self-renewal and commitment to various differentiation pathways. * **Metabolic Priming and Energy Homeostasis:** The profile includes genes central to cellular metabolism and energy production, such as [GAPDH](/details-gene/2597) (glycolysis), [SLC25A6](/details-gene/293) (mitochondrial ATP/ADP transport), and [COX7C](/details-gene/1350) (cytochrome c oxidase). Their specificity suggests that MSCs maintain a high basal metabolic rate, providing the necessary energy and building blocks for proliferation and differentiation. * **Calcium Signaling and Cellular Dynamics:** High specificity is observed for genes involved in calcium signaling and cytoskeletal organization, such as [S100A6](/details-gene/6277), a calcium-binding protein, and [CFL1](/details-gene/1072) (cofilin 1), an actin-depolymerizing factor. Notably, [SARAF](/details-gene/51669), a negative regulator of store-operated calcium entry, is a top marker (CSI: 7.10), suggesting that precise control of calcium influx is a defining characteristic, potentially to maintain an undifferentiated state. * **Immunomodulation and Stress Response:** Genes such as [MIF](/details-gene/4282) (macrophage migration inhibitory factor) and [HMGB1](/details-gene/3146) are specifically expressed. [MIF](/details-gene/4282) is a key immunomodulatory cytokine, while [HMGB1](/details-gene/3146) acts as a damage-associated molecular pattern (DAMP), consistent with the known roles of MSCs in tissue repair and inflammation modulation. The specificity of ferritin light and heavy chains ([FTL](/details-gene/2512) and [FTH1](/details-gene/2495)) may also point to a role in managing iron homeostasis and oxidative stress. **Overall**, the anti-marker profile reinforces the undifferentiated nature of these cells. The low specificity for genes involved in committed developmental pathways, such as [BMP4](/details-gene/652), [FST](/details-gene/10468) (Follistatin), and the transcription factor [HOXC10](/details-gene/3226), indicates that MSCs in their basal state are not actively pursuing a specific lineage fate. ## Clinical Significance and Contextual Roles The gene significance profile of [mesenchymal stem cells](/details-cell/CL0000134) provides insights into their therapeutic potential and involvement in disease. Their inherent capacity for high biosynthetic activity and immunomodulation forms the basis of their application in regenerative medicine. The specific expression of immunomodulatory molecules like [MIF](/details-gene/4282) and the DAMP protein [HMGB1](/details-gene/3146) provides a molecular rationale for the observed ability of MSCs to suppress inflammation and promote tissue healing. These functions are being actively explored in clinical trials for conditions such as graft-versus-host disease, osteoarthritis, and autoimmune disorders. The high specificity of iron-managing proteins [FTL](/details-gene/2512) and [FTH1](/details-gene/2495) suggests a role in controlling local inflammatory environments, as iron availability is critical for both host and pathogen responses. From a pathology perspective, the machinery that enables MSC function can be hijacked during carcinogenesis. [NPM1](/details-gene/4869), the top marker for MSCs, is frequently mutated in acute myeloid leukemia ([Link](https://pubmed.ncbi.nlm.nih.gov/2713355/)), suggesting a potential link between the fundamental biology of stem cells and the development of hematological malignancies. Similarly, [HMGB1](/details-gene/3146) is overexpressed in various cancers and contributes to tumor growth and metastasis ([Link](https://pubmed.ncbi.nlm.nih.gov/9036861/)). This highlights that the very pathways defining MSC identity can also be implicated in disease when dysregulated. ## Potential Mechanisms and Research Directions 1. **Hypothesis: The multipotent state of MSCs is maintained by a tightly regulated, high-flux biosynthetic system centered on ribosome biogenesis and post-transcriptional control.** The exceptional specificity of genes like [NPM1](/details-gene/4869), [NCL](/details-gene/4691), and numerous hnRNPs suggests that the rate and fidelity of protein synthesis are not merely housekeeping functions but are central pillars of MSC identity. This system may act as a master regulator, enabling rapid responses to differentiation cues while preventing spontaneous commitment. * **Surprising Finding:** The discovery that such ubiquitous cellular machinery components are the most *specific* markers for MSCs is counterintuitive. It implies that MSCs are uniquely dependent on the efficiency of these pathways, perhaps acting as a critical checkpoint for maintaining pluripotency and executing differentiation programs effectively. * **Testable Question:** How does shRNA-mediated knockdown of [NPM1](/details-gene/4869) versus a lineage-specific transcription factor (e.g., RUNX2 for osteogenesis) differentially affect the global translatome and the ability of MSCs to undergo tri-lineage differentiation? 2. **Hypothesis: Precise control of intracellular calcium levels, particularly the prevention of excessive influx via store-operated calcium entry (SOCE), is a critical mechanism for preserving MSC quiescence and immunomodulatory potential.** The high specificity of [SARAF](/details-gene/51669), a known inhibitor of SOCE, alongside calcium-binding protein [S100A6](/details-gene/6277) and the immunomodulator [MIF](/details-gene/4282), suggests an integrated signaling axis where calcium homeostasis dictates the cell's response to inflammatory signals. * **Surprising Finding:** The prominence of a negative regulator of calcium signaling ([SARAF](/details-gene/51669)) as a top cell type marker is unexpected. It shifts the focus from calcium signaling activation to the active maintenance of a low-calcium state as a defining feature, possibly to prevent premature activation or differentiation. * **Testable Question:** Does CRISPR-mediated knockout of [SARAF](/details-gene/51669) in MSCs lead to increased basal intracellular calcium, spontaneous differentiation, and an altered secretome profile, particularly affecting the release of immunomodulatory factors like [MIF](/details-gene/4282) in co-culture with activated T-cells?