Details for: CL0000557

Cell ID: CL0000557

Cell Name: granulocyte monocyte progenitor cell

Description: Originally described in the dendritic cell ontology (DC_CL:0000042)(PMID:19243617). GMPs are reportedly CD16-positive, CD32-positive, CD34-positive, CD38-positive, CD45RA-positive, CD110-negative, CD117-positive, CD123-positive, and SCA1-negative.

Synonyms: granulocyte/monocyte precursor, granulocyte/monocyte progenitor, CFU-C , Colony forming unit in culture, CFU-GM, GMP, colony forming unit granulocyte macrophage, granulocyte-macrophage progenitor

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 granulocyte monocyte progenitor 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 granulocyte monocyte progenitor 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 granulocyte monocyte progenitor 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 granulocyte monocyte progenitor 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:  granulocyte monocyte progenitor cell (CL0000557)

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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 [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (GMP) is a multipotent hematopoietic precursor that gives rise to mature [granulocytes](/details-cell/CL0000094) and [monocytes](/details-cell/CL0000576). Phenotypically, these cells are described by the presence of surface markers such as CD34, CD38, CD117, and CD123. Transcriptomic analysis reveals that the most defining characteristic of GMPs, based on expression specificity (**Overall**), is an exceptionally high level of activity in fundamental cellular processes. The top marker genes are overwhelmingly involved in core metabolic pathways (glycolysis and oxidative phosphorylation), chromatin organization, and protein synthesis. This signature suggests that the GMP identity is characterized by a state of high biosynthetic and metabolic readiness, which is essential for its function in rapid proliferation and subsequent differentiation into mature myeloid lineages. ## Key Characteristics and Function The gene significance profile of the [granulocyte monocyte progenitor cell](/details-cell/CL0000557) is dominated by genes essential for cellular infrastructure and energy production, indicating a state primed for division and differentiation. * **High Metabolic Activity:** A prominent functional cluster of top markers is dedicated to energy metabolism. This includes [GAPDH](/details-gene/2597), a key enzyme in glycolysis, as well as multiple components of the mitochondrial respiratory chain, such as [COX4I1](/details-gene/1327), [COX7C](/details-gene/1350), [COX5B](/details-gene/1329), and subunits of ATP synthase like [ATP5MC2](/details-gene/517) and [ATP5MG](/details-gene/10632). The high specificity score (`csi_z`) for these genes suggests that an elevated rate of both aerobic and anaerobic respiration is a defining feature of GMPs, providing the necessary ATP to fuel the demanding processes of hematopoiesis. * **Active Chromatin and Gene Regulation:** GMPs exhibit high expression of genes involved in chromatin architecture and RNA processing. [HMGB1](/details-gene/3146), the top marker, is a non-histone chromatin protein involved in DNA bending and transcriptional regulation [Link](https://pubmed.ncbi.nlm.nih.gov/8661151/). The histone variant [H2AZ1](/details-gene/3015) is associated with transcriptional regulation and maintaining chromatin plasticity [Link](https://pubmed.ncbi.nlm.nih.gov/1697587/). Furthermore, a suite of heterogeneous nuclear ribonucleoproteins ([HNRNPU](/details-gene/3192), [HNRNPA2B1](/details-gene/3181), [HNRNPA1](/details-gene/3178)) and other RNA-binding proteins ([YBX1](/details-gene/4904), [PABPC1](/details-gene/26986)) are highly significant, pointing to extensive post-transcriptional regulation and mRNA processing, likely to support a diverse and dynamic proteome. * **Robust Protein Synthesis and Maintenance:** The machinery for protein translation and quality control is highly active. High significance is noted for eukaryotic translation elongation factors [EEF1D](/details-gene/1936) and [EEF1B2](/details-gene/1933). Additionally, [NPM1](/details-gene/4869), a nucleolar phosphoprotein involved in ribosome biogenesis, is a key marker [Link](https://pubmed.ncbi.nlm.nih.gov/2478125/). The high expression of [FTL](/details-gene/2512), which encodes the ferritin light chain, underscores the cell's requirement for iron, a critical cofactor for metabolic enzymes and DNA synthesis. * **Defining by Absence (Anti-Markers):** The genes with the lowest significance scores (anti-markers) are often associated with more specialized or terminally differentiated cell functions. For example, the low significance of [KIF15](/details-gene/56992) (a kinesin-like protein) and transcription factors like [ELK1](/details-gene/2002) suggests that while these processes occur, they are not the defining, unusually active pathways that characterize the GMP state. The low score for [FUT7](/details-gene/2529), an enzyme critical for synthesizing sialyl Lewis x for leukocyte tethering [Link](https://doi.org/10.1016/s0021-9258(17)36686-3), indicates a lack of commitment to the mature, migratory granulocyte phenotype. ## Clinical Significance and Contextual Roles Although this analysis is based on an **Overall** context without a direct disease comparison, the key marker genes of [granulocyte monocyte progenitor cells](/details-cell/CL0000557) have profound clinical relevance, particularly in hematologic malignancies. The high metabolic state defined by markers like [GAPDH](/details-gene/2597) and COX family genes is a hallmark of many cancer cells, which rely on elevated energy production to sustain rapid growth. The reliance of GMPs on these pathways may represent a vulnerability that could be exploited therapeutically. Several top markers are directly implicated in cancer. Mutations in [NPM1](/details-gene/4869) are among the most common genetic alterations in acute myeloid leukemia (AML), a cancer of the myeloid line of blood cells. The high expression of [NPM1](/details-gene/4869) in normal GMPs may provide a context for its oncogenic role when mutated. Similarly, [HMGB1](/details-gene/3146) can be released by cells and act as a damage-associated molecular pattern (DAMP), promoting inflammation and tumorigenesis in various contexts [Link](https://doi.org/10.1002/(sici)1097-0215(19970220)74:1%3C1::aid-ijc1%3E3.0.co;2-6). The constitutive high expression in GMPs suggests a potential role in regulating the bone marrow microenvironment under normal and pathological conditions. The strong signature of RNA-binding proteins like [HNRNPA1](/details-gene/3178) is also relevant, as their dysregulation is frequently observed in cancers, affecting splicing and mRNA stability of key oncogenes and tumor suppressors. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The identity of the [granulocyte monocyte progenitor cell](/details-cell/CL0000557) is primarily defined by a state of "metabolic overdrive" rather than a unique set of lineage-determining transcription factors. This heightened basal activity of core biosynthetic and energy-producing pathways is essential to maintain the multipotency and proliferative capacity required for replenishing the myeloid compartment. * **Surprising Findings:** The most specific gene markers for this progenitor cell are not surface antigens or classic hematopoietic transcription factors, but rather ubiquitous housekeeping genes like [HMGB1](/details-gene/3146) and [GAPDH](/details-gene/2597). The analysis suggests that it is the *quantitative rate* of these fundamental processes, not the simple presence of a unique protein, that most distinguishes GMPs from other cells in this dataset. * **Testable Questions:** How does the metabolic flux through glycolysis versus oxidative phosphorylation in GMPs compare to that in downstream progeny ([monocytes](/details-cell/CL0000576) and [neutrophils](/details-cell/CL0000775))? Furthermore, would targeted inhibition of ATP synthase (e.g., using oligomycin) or glycolysis (e.g., using 2-deoxyglucose) preferentially induce apoptosis or differentiation arrest in GMPs compared to more mature myeloid cells? 2. **Hypothesis:** The high expression of chromatin-modifying ([H2AZ1](/details-gene/3015)) and RNA-processing proteins ([HNRNPU](/details-gene/3192), [YBX1](/details-gene/4904)) establishes a state of "transcriptional plasticity." This poised epigenetic and post-transcriptional landscape allows GMPs to rapidly and efficiently execute either granulocytic or monocytic differentiation programs in response to specific cytokine signaling, without requiring de novo synthesis of the entire regulatory machinery. * **Surprising Findings:** The gene profile is notably enriched for factors that *manage* the flow of genetic information (chromatin remodelers, splicing factors, RNA-binding proteins) rather than factors that *direct* lineage commitment (e.g., PU.1 or C/EBPα, which are expected but not the top specificity markers here). This suggests the cell's defining program is one of readiness and potential, rather than active differentiation. * **Testable Questions:** If [YBX1](/details-gene/4904) or [HNRNPU](/details-gene/3192) are knocked down in primary human GMPs, does this skew differentiation towards one lineage (granulocyte vs. monocyte) upon stimulation with a combination of cytokines? Additionally, does a RIP-seq (RNA immunoprecipitation sequencing) analysis of HNRNPU reveal binding to distinct sets of pre-mRNAs that are critical for subsequent granulocytic versus monocytic fate decisions?