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The blood and immune cell-specific proteomeThe blood and immune cell transcriptomeMast cellsNeutrophilsMononuclear phagocytesT-cellsInnate lymphoid cellsB-cellsPlasma cellsDendritic cellsNK-cellsMegakaryocytesPlateletsErythrocytesOther Blood and immune cellDeep Visual Proteomics analysis of blood and immune cellNeutrophilsMacrophagesT-cells B-cellsBlood and immune cell functionBackgroundRelevant links and publications
Single cell type methods
DVP methods
The blood and immune cell-specific proteomeBlood & immune cells develop from hematopoietic stem cells (HSCs), which are multipotent cells with the ability to self-renew that can differentiate into all types of blood cells included in the lymphoid and the myeloid lineage. These cells reside in the medullary region of the bone marrow. Mature blood cells and immune cells circulate in the blood, and certain immune cells also reside within different tissues, e.g. liver and placenta. Transcriptome analysis shows that 67% (n=13603) of all human proteins (n=20162) are detected in blood and immune cells and 3499 of these genes show an elevated expression in any blood and immune cells compared to other cell type groups. In-depth analysis of the elevated genes in blood and immune cells using scRNA-seq and antibody-based protein profiling allowed us to visualize the expression patterns of these proteins in the following types of blood and immune cells: Mast cells, Neutrophil progenitors, Neutrophils, Monocyte progenitors, Monocytes, Kupffer cells, Hofbauer cells, T-cells, Thymocytes, Innate lymphid cells, B-cells, plasma cells, Dendritic cells, NK-cells, Megakaryocytes and platelets. In addition, we utilized proteomic data from a mass spectrometry (MS)-based, cell type–resolved atlas of the human body, generated via Deep Visual Proteomics (DVP), a spatial proteomics platform that combines imaging-guided cell selection with high-resolution protein analysis. The analysis includes several blood and immune cell types, including neutrophils from bone marrow, as well as macrophages, T-cells and B-cells from lymph node. Out of a total of 14361 detected proteins in all cell types, 8325 were detected in at least one of the blood and immune cell types, and 2094 were classified as elevated in at least one blood and immune cell types. Further details on cell type specific proteome profiles, as well as examples of enriched proteins across different blood and immune cells, are provided below. The blood and immune cell transcriptomeThe scRNA-seq-based blood and immune cell transcriptome can be analyzed with regard to specificity, illustrating the number of genes with elevated expression in each specific blood and immune cell type compared to other cell types (Table 1). Genes with an elevated expression are divided into three subcategories:
Expression profiles are compared across the 154 cell types, in addition to the comparison across the 53 grouped cell types. This results in cell specificity categories based on two datasets, one more detailed across all cell types and one more suitable for the general overview based on the grouped cell types with similar expression profile and functions. Cell types are grouped based on function and biology, to facilitate a better overview and to complement the detailed information based on all cell types. Below you can find tables for each cell type group with genes classified as elevated in the respective cell type, compared to all other cell types.
Mast cellsMast cells are granulated immune cells that release histamine and mediators upon activation. They participate in allergy, parasite defense, and tissue remodeling. The blood granulocyte population includes eosinophils, basophils and neutrophils, the latter being the most abundant type, while mast cells are tissue resident granulocytes found in most parts of the body near mucosal tissues.
As shown in the table, 375 genes show elevated expression in mast cells compared to other cell types. Membrane spanning 4-domains A2 (MS4A2) is a subunit of a membrane receptor in basophils and mast cells that binds to the FC region of IgE antibodies in order to enable the degranulation response where enzymes and other pro-inflammatory mediators are released to fight infection. One such enzyme is tryptase alpha/beta 1 (TPSAB1), a neutral protease involved in the activation of connective tissue cells.
NeutrophilsNeutrophils are considered the first line of defence in the innate immune system, and are involved in the healing of damaged tissues and the defence against infections. They are the most abundant leukocytes in the circulation and capture and destroy invading micro-organisms by phagocytosis, release of bactericidal and protein-destroying compounds from the granules, and by the generation of neutrophil extracellular traps (NETs), but they also participate as mediators of inflammation. As shown in table 1, 1447 genes show elevated expression in neutrophils compared to other grouped cell types. Neutrophils as a grouped cell type, includes both neutrophile progenitor cells as well as neutrophils, which is also used for cell type- specificity categories.
Mononuclear phagocytesMononuclear phagocytes, including monocyte progenitors, monocytes, and macrophages, are widely distributed across tissues and play essential roles in immune surveillance and homeostasis. Monocyte progenitors originate in the bone marrow, while mature monocytes circulate in the blood and various organs. Macrophages, found in nearly all tissues, exhibit strong tissue-specific specialization, such as Kupffer cells in the liver and Hofbauer cells in the placenta.
MonocytesAs shown in Table 1, 677 genes are elevated in monocytes compared to other cell types. Monocytes compose 2-10% of all white blood cells in the human body. The proliferation takes place in the bone marrow and then circulates the bloodstream until they migrate to tissues and body cavities where they are differentiated into macrophages and dendritic cells. They also possess antimicrobial functions. Ficolin-1 (FCN1) is a member of the complement system and binds pathogen associated molecular patterns on microbes.
MacrophagesAs shown in Table 1, 493 genes are elevated in macrophages compared to other cell types. Macrophages belong to a group of white blood cells called phagocytes, which is a type of cells specialized in phagocytosis, a process that protects the body by ingesting cellular debris, dead cells or pathogens. Mature macrophages are found throughout the body in most tissues, they do not travel far and are rarely seen in the bloodstream, instead they are guarding locally and waiting to be activated. Macrophage polarization is a process where they adopt different functions depending on the signals received from the environment and the two major states are the M1(pro-inflammatory) and the M2(anti-inflammatory). Macrophage scavenger receptor 1 (MSR1) encodes a receptor on the macrophage cell surface that has a homeostatic function by clearing modified lipids and proteins.
Hofbauer cellsAs shown in Table 1, 580 genes are elevated in Hofbauer cells compared to other cell types. Hofbauer cells are fetal macrophages that can be found in the villous stroma at all stages of gestation. The term is used for any fetal derived macrophages in the placental villous core, amnion and chorionic lavae. They have several proposed functions including preventing vertical transmission, i.e transmission from the mother to the fetus, being pro-angiogenic and playing a role in placental morphogenesis. V-set immunoglobulin-domain-containing 4 (VSIG4) is a protein that is expressed in Hofbauer cells. It is a phagocytic receptor, a strong negative regulator of T-cell proliferation and IL2 production, and a potent inhibitor of the alternative complement pathway convertases.
Kupffer cellsAs shown in Table 1, 599 genes are elevated in Kupffer cells compared to other cell types. Kupffer cells are part of the innate immune defense in the liver, they are specialized macrophages lining the liver sinusoidal endothelial walls and filter the blood from microbial debris and particles which enter through the hepatic portal vein. Kupffer cells make up to 80-90% of all macrophages in the body and their function and structures differ depending on if they reside in the centrilobular or periportal region. Macrophage receptor with collagenous structure (MARCO) is a protein expressed on macrophages including Kupffer cells that may bind both gram-positive and gram-negative bacterias.
T-cellsT-cells or T-lymphocytes are a type of lymphocyte that is a part of the adaptive immune system together with B-cells.
ThymocytesThymocytes are immature T cells located in the thymus, where they undergo several tightly regulated developmental stages before becoming functional T cells. As shown in the table, 340 genes show elevated expression in thymocytes compared to other cell types. T-cellsOnce thymocytes successfully mature, they leave the thymus and enter the bloodstream and lymphoid organs as T cells. These are the functional units of the adaptive cellular immune response. As shown in the table, 439 genes show elevated expression in T-cells compared to other cell types. An example of a protein with elevated expression is T-cell surface glycoprotein CD8 beta chain (CD8B) which is the beta chain of the cell surface glycoprotein CD8 and is an important molecule mediating cell-cell interactions in the lymphoid tissues. Acting as a coreceptor to the T-cell receptor on the T-cell, it recognizes MHC class I molecules displayed by an antigen-presenting cell.
Innate lymphoid cellsILCs are a family of innate immune cells that resemble lymphocytes (like T cells) in function and morphology, but lack antigen-specific receptors (they don’t have T-cell receptors or B-cell receptors). They provide a rapid first line of defense and help shape the adaptive immune response. As shown in the table, 322 genes show elevated expression in tnnate lymphoid cells compared to other cell types.
B-cellsB-cells or B-lymphocytes are a type of white blood cell of the lymphocyte subtype, that mature in the bone marrow. They express B-cell receptors on their surface that allow them to bind specific antigens, and function in the humoral immunity component of the adaptive immune system by secreting antibodies.
Plasma cellsPlasma cells are a large type of lymphocytes that originate in the lymphoid organs as B-cells, with the function to produce large quantities of antibodies by internalizing antigens through receptor-mediated endocytosis. When the B-cell breaks down the antigen, bits of pieces of the antigen called antigenic peptides are presented on the surface through MHCII molecule, where it can be activated by a T-cell to differentiate into specific cells, in this case a plasma cell.
Dendritic cellsDendritic cells are antigen-presenting cells present in tissues that are in contact with the external environment, e.g. skin, but also in an immature state in the blood, and upon activation they migrate to the lymph nodes to interact with T-cells and B-cells. They act as messengers between the innate and the adaptive immune systems. As shown in Table 1 (above) 364 genes show elevated expression in dendritic cells compared to other grouped cell types. Dendritic cells as a group includes both conventional DCs and plasmacytoid DCs, specialized immune cells that act as sentinels of the immune system.
Conventional dendritic cellsThey are the primary antigen-presenting cells (APCs) that activate T cells. Includes cDC1, specialize in activating CD8⁺ cytotoxic T cells (important for antiviral and anti-tumor responses) and cDC2, specialize in activating CD4⁺ helper T cells (important for coordinating immune responses, especially against bacteria and fungi). As shown in the table 514 genes show elevated expression in cDC compared to other cell types Plasmacytoid cendritic cellsThey are the major producers of type I interferons (IFN-α and IFN-β), cytokines that play a crucial role in antiviral defense. pDCs can also present antigens, though less efficiently than cDCs. As shown in the table 411 genes show elevated expression in pDC compared to other cell types An example of a protein with elevated expression in pDC is interferon regulatory factor 7 (IRF7), an important transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the immune response against DNA and RNA viruses.
NK-cellsNatural killer cells (NK-cells) are a type of cytotoxic lymphocyte that circulate in the blood. As a critical part of the innate immune system, they patrol the body and, upon contact with virus-infected cells, tumor formation and stressed cells, respond rapidly by releasing cytotoxic granules that destroy the target cell(s).
MegakaryocytesMegakaryocytes are large bone marrow cells responsible for producing platelets (thrombocytes) — the small cell fragments essential for blood clotting and wound repair.
Megakaryocyte progenitorsMegakaryocyte progenitors are intermediate precursor cells derived from the common myeloid progenitor (CMP) that are committed specifically to the megakaryocytic lineage. They proliferate and begin early differentiation toward mature megakaryocytes under the influence of growth factors. As shown in the table, 417 genes show elevated expression in Megakaryocyte progenitors compared to other cell types. Magakaryocyte-Erythroid progenitorsMEPs are bipotent progenitor cells that can give rise to both megakaryocytes and erythrocytes (red blood cells). They represent a critical branching point in hematopoiesis, where the decision between platelet and red blood cell production occurs. As shown in the table, 0 genes show elevated expression in Magakaryocyte-Erythroid progenitors compared to other cell types. MegakaryocytesMegakaryocytes are large, polyploid bone marrow cells responsible for producing platelets, which are essential for blood clotting and wound repair. They extend cytoplasmic projections called proplatelets into bone marrow sinusoids, where platelets are released into circulation. As shown in the table, 517 genes show elevated expression in Megakaryocytes compared to other cell types. Majority of genes with elevated expression in megakaryocytes are shared with platelets, such is the case for platelet factor 4 (PF4), a protein released from active platelets, which is involved in platelet aggregation.
PlateletsPlatelets are produced by megakaryocytes in the bone marrow and are released to the circulating blood. Their main role is to initiate blood clot formation in response to blood vessel injury. In addition, they have possible roles in the regulation of immunity and inflammation. As shown in the table, 517 genes show elevated expression in Megakaryocytes compared to other cell types.
A protein expressed on the surface of platelets is platelet glycoprotein IX (GP9), which allows attachment to damaged blood vessels.
ErythrocytesErythrocytes are biconcave cells specialized for oxygen transport throughout the body via the protein hemoglobin. They are the most abundant blood cells, optimized for gas exchange and flexibility to travel through capillaries. As shown in Table 1, 326 genes show elevated expression in erythroid cells compared to other groups of cell types.
Erythrocyte progenitorsErythrocyte progenitors are developing red blood cell precursors derived from megakaryocyte–erythroid progenitors (MEPs). They mature through stages including proerythroblast → basophilic → polychromatic → orthochromatic erythroblast, eventually losing their nucleus to become reticulocytes and then mature erythrocytes. As shown in the table, 508 genes show elevated expression in erythrocyte progenitors compared to other cell types. ErythrocytesErythroid cells, also called erythrocytes or red blood cells, acquire oxygen from the inhaled air in the lungs and transport the oxygen to all tissues of the body via the circulatory system. As shown in the table, 93 genes show elevated expression in Erythrocytes compared to other cell types. Hemoglobin subunit beta HBB and subunit delta HBD are components of the hemoglobin molecule which is expressed exclusively in erythroid cells and bind oxygen.
Other Blood and immune cell
Langerhans cellsLangerhans cells are dendritic cells that originate from bone marrow progenitors and have their function in the epidermis of the skin, where they represent as the first line of immunologic defense. Like macrophages, LCs present antigens to lymphocytes through different surface receptors and are able to regulate innate and adaptive responses. In the Cell Type Resource Langerhans cells are represented by too few cells, number under our cut off, and therefore not included in the cell type classification. However, the positive cells are still shown and genes specifically expressed in Langerhans cells show the expected profile. One well-known surface receptor is langerin (CD207). Cluster of Differentiation 1a (CD1A) is a transmembrane glycoprotein with structural similarities to MHC class I. CD1A mediates primarily lipid-based antigens to T-cells.
Deep Visual Proteomics analysis of blood and immune cellProteomic data from a mass spectrometry (MS)-based, cell type–resolved atlas of the human body, generated via Deep Visual Proteomics (DVP), a spatial proteomics platform that combines imaging-guided cell selection with high-resolution protein analysis, is integrated to the Single Cell Type resrouce. This enables exploration of global protein detection profiles with RNA expression profiles. The DVP data includes 13496 detected proteins and covers 27 cell types which is grouped into 24 main cell types used for classification and the RNA comparison. The cell type specificity categories were applied to the protein data. Here, we describe the included blood and immune cell and show examples of proteins with elevated detection. NeutrophilsDVP resulted in 757 proteins classified as elevated in Neutrophils. In total, 5537 proteins were detected in Neutrophils, out of these, 65 were only detected in neurons, compared to the other 23 DVP samples. A bone marrow smear sample was used together with MCEMP1 labelling, cells with strong positivity was selected and here represent bone marrow neutrophiles. The 184 genes classified as enriched in bone marrow neutrophils reflect a developing and highly specialized innate immune program associated with granulocyte maturation, antimicrobial defense, and rapid inflammatory responses. One group of proteins, including MPO, CTSG, PRTN3, and BPI, represents the azurophilic granule machinery responsible for pathogen killing through oxidative and proteolytic mechanisms, highlighting the acquisition of potent antimicrobial effector functions during neutrophil development in the bone marrow. A second set of proteins, including CAMP, MMP8, MMP9, and S100A8, is linked to inflammatory signaling, extracellular matrix remodeling, and recruitment to damaged or infected tissues, reflecting the readiness of mature neutrophils for migration and rapid innate immune activation following release from the bone marrow. Mast Cell Expressed Membrane Protein 1 (MCEMP1) was the marker used for labelling myeloid-lineage-associated cells of the bone marrow, and cells with strong singnal was singled out for the DVP data, resulting in a neutrophil enriched, but not limited to, profile. MacrophagesDVP resulted in 661 proteins classified as elevated in Macrophages. In total, 7320 proteins were detected in Macrophages, out of these, 192 were only detected in Macrophages, compared to the other 23 DVP samples. The 83 macrophage enriched proteins includes a set of scavenging, antigen-presenting, and immunoregulatory proteins, including CD163, CD163L1, CD14, MARCO, TIMD4, and CLEC10A, consistent with roles in uptake and clearance of cellular debris and glycoproteins. In addition, increased CD86 and IL2RA expression suggests an activated immune-interacting state, while F13A1 enrichment reflects a tissue-resident macrophage program linked to extracellular matrix remodeling and hemostatic regulation. T-cellsDVP resulted in 965 proteins classified as elevated in T-cells. In total, 7305 proteins were detected in T-cells, out of these, 55 were only detected in T-cells, compared to the other 23 DVP samples. The 118 T-cell enriched proteins include canonical components of the T cell receptor signaling complex such as CD3D, CD3E, CD3G, CD247, ZAP70, and TRAT1, together with CD6 and the signaling adaptors SH2D1A and SH2D2A, consistent with active T cell receptor engagement and downstream activation. A strong cytotoxic CD8+ T cell program is indicated by CD8A expression alongside effector molecules CTSW, GZMK, and GZMM, reflecting cytotoxic effector functions and target cell killing activity. In parallel, elevated CD4 expression in the broader immune-enriched set suggests contributions from CD4+ T cell and other CD4-expressing immune populations. This is often accompanied by helper T cell–associated or broader immune regulatory markers such as IL7R, which are typically linked to naïve or central memory CD4+ T cells and immune coordination rather than direct cytotoxicity. CD8+ T-cells resulted in several expected proteins with elevated detection. However, the CD4+ T-cell samples struggels to deliver the expected protein profile B-cellsDVP resulted in 520 proteins classified as elevated in B-cells. In total, 6461 proteins were detected in B-cells, out of these, 17 were only detected in B-cells, compared to the other 23 DVP samples. The 27 B-cell enriched proteins include the canonical B cell lineage markers MS4A1 (CD20) and CD79A, confirming a mature B cell population. This signature is accompanied by FCGR2B, an inhibitory Fc receptor that regulates immune complex–driven activation and is characteristic of B cell immune modulation. Elevated CD70 suggests an activated B cell state with increased costimulatory potential, while increased GPR65 (HSPA5) reflects endoplasmic reticulum stress and heightened protein-folding demand, consistent with increased biosynthetic or secretory activity. Together, these features indicate a mature B cell compartment with both regulatory and activated states, potentially including cells transitioning toward antibody-secreting phenotypes. Blood and immune cell functionThe blood has many important functions including oxygen/carbon dioxide transport, removal of waste, coagulation, and body temperature regulation etc. Blood that accounts for about 7% of the human body weight circulates the body through blood vessels and is synthesized in the hematopoiesis process. The HSCs can give rise to all blood cells including; B-lymphocytes, T-lymphocytes, natural killer cells, granulocytes, monocytes, erythrocytes, and platelets. Studies have suggested two models for hematopoiesis: deterministic or stochastic. In the deterministic model, it is suggested that different factors in the hematopoietic microenvironment decide what the HSCs should differentiate into. In the stochastic model, the HSCs differentiate into the specific blood cells by randomness. In addition to antibody production in response to contact with antigens, B-cells are also classical antigen-presenting cells and secrete cytokines. Naive B lymphocytes reside in lymph nodes and have not yet been exposed to an antigen. Upon antigen activation they will differentiate to either plasma cells or memory B-cells. Memory B lymphocytes are formed within germinal centers following primary infection, and are important in generating an accelerated and more robust antibody-mediated immune response in the case of re-infection. They are localized in areas of facilitated antigen encounter and compared to naive B-cells they have a higher affinity to the immunizing antigen, a lifespan of decades instead of weeks, and faster and more efficient proliferation and differentiation. T-cells originate from hematopoietic cells in the bone marrow, which develop into immature thymocytes in the thymus. The thymocytes differentiate into several types of mature T-cells; T-helper cells, cytotoxic T-cells, memory T-cells, regulatory T-cells and natural killer T-cells. During maturation, T-cells undergo β-selection and positive selection in the thymic cortex and negative selection in the thymic medulla. The histology of organs that contain blood and immune cells, including interactive images, is described in the Protein Atlas Histology Dictionary. BackgroundHere, the protein-coding genes expressed in blood and immune cells are described and characterized, together with examples of immunohistochemically stained tissue sections that visualize corresponding protein expression patterns of genes with elevated expression in different blood and immune cell types. The transcript profiling was based on publicly available genome-wide expression data from scRNA-seq and snRNA-seq experiments (36 datasets) covering 34 tissues. All datasets (unfiltered read counts of cells) were clustered independenty using leiden clustering, resulting in a total of 1175 different cell type clusters. The clusters were then manually annotated based on a survey of known tissue and cell type-specific markers. The RNA-seq data from each cluster of cells was aggregated to mean normalized protein-coding counts per million (nCPM) for all protein-coding genes. A specificity and distribution classification was performed for both single cell types individually, as well as grouped into 53 main cell type groups. The specificity classification determined the number of elevated genes, while the distribution determined whether genes are detected in one, several or all cell types or cell type groups. It should be noted that since the analysis was limited to datasets representing 34 tissue types, not all human cell types are represented. Furthermore, some cell types are present only in low amounts, or identified only in mixed cell clusters, which may affect the results and bias the cell type specificity. Relevant links and publications Uhlén M et al., Tissue-based map of the human proteome. Science (2015) |
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