The spleen cell type enriched transcriptome

The spleen is a multifunctional organ that plays crucial roles in the immune system and blood filtration. The spleen is typically divided into red pulp and white pulp, the red pulp contains sinusoids which act as a blood filter, removing old and damaged red blood cells from circulation, whereas the white pulp consists entirely of lymphoid tissue. Additionally, the spleen recycles iron from old red blood cells and serves as a site for the production and storage of monocytes and red blood cells. While not essential for survival, as other organs can take over its functions, the spleen contributes significantly to maintaining overall health and fighting infections.

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2668 genes were predicted to have cell type specificity in the spleen.

  • 14 cell types profiled
  • 719 very highly enriched genes
  • 892 highly enriched genes
  • 1065 moderately enriched genes

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Spleen cell type enriched transcriptome: Summary

Genes with predicted cell type specificity within spleen are detailed in Table 1. Identified genes are subdivided into 3 specificity categories, based on the difference between the enrichment score in the corresponding cell type, compared to the other cell types profiled in the tissue (see Methods Summary page for details):

  • Predicted specificity: ยดVery highยด - Differential score vs. other profiled cell types within the tissue >0.35
  • Predicted specificity: ยดHighยด - Differential score vs. other profiled cell types within the tissue >0.25
  • Predicted specificity: ยดModerateยด - Differential score vs. other profiled cell types within the tissue >0.15


Table 1. Number of genes in each specificity category in the spleen cell types.

Cell type
Very high
High
Moderate
Total enriched
Mitotic cells (Spleen) 163 36 16 215
Platelets 16 4 2 22
Erythrocytes 21 18 8 47
Hematopoietic stem cells 11 5 20 36
B-cells (Spleen) 102 145 196 443
NK-cells (Spleen) 3 4 12 19
Endothelial cells 25 167 173 365
Smooth muscle cells 13 21 27 61
Fibroblasts 34 141 337 504
Macrophages 105 98 81 284
Neutrophils 160 102 86 348
T-cells 20 59 49 128
Plasma cells 46 92 58 196
All cell types 7198921065 2668


Figure 1. Bar plot of the number of enriched genes in the cell types of the spleen, divided by specificity category

0.050100150200250300350400genesMitotic cells (Spleen)PlateletsErythrocytesHematopoietic stem cellsB-cells (Spleen)NK-cells (Spleen)Endothelial cellsSmooth muscle cellsFibroblast_1Fibroblast_2MacrophagesNeutrophilsT-cellsPlasma cellsVery highHighModerate

Spleen cell type enriched transcriptome: Illustrative examples

Red pulp

The red pulp is the primary component of the spleen, making up about 75-80% of its tissue. It consists of a network of splenic cords and venous sinuses filled with blood. The red pulp's main functions include filtering blood to remove old or damaged red blood cells, storing platelets and monocytes, and recycling iron from hemoglobin. Specialized macrophages in the red pulp phagocytose worn-out erythrocytes and pathogens. The unique structure of the red pulp, with its narrow passageways, allows for mechanical filtration of blood cells and the trapping of abnormal or aged cells.

Endothelial cells

The spleen contains endothelial cells from both normal blood vessel, as well as specialised sinusoids that assist in the filtering of blood to remove old and damaged red blood cells, or erythrocytes. Genes classified as having specificity in endothelial cells of the spleen include and the Adhesion G protein-coupled receptor L4 (ADGRL4) and Phosphatidylinositol Transfer Protein, Membrane-Associated 3 (PITPNM3).

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ADGRL4 - spleen

ADGRL4
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PITPNM3 - spleen

PITPNM3

Erythrocytes

Erythrocytes (red blood cells) are biconcave, anucleate cells filled with hemoglobin that primarily function to transport oxygen from the lungs to body tissues and carbon dioxide from tissues back to the lungs. In the spleen, older or damaged erythrocytes are filtered out and phagocytosed by macrophages in the red pulp, while the iron from their hemoglobin is recycled for use in new red blood cell production. Erythrocyte genes Hemoglobin subunit alpha 1 (STAB2), and Bisphosphoglycerate mutase (BPGM) are important in the regulation of hemoglobin oxygen affinity.

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HBA1 - spleen

HBA1
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BPGM - spleen

BPGM

Platelets

Platelets are small, anucleate cells in the blood that play a crucial role in hemostasis by forming clots to stop bleeding when blood vessels are damaged. The spleen stores about one-third of the body's platelets, acting as a reservoir that can release them into circulation when needed. Additionally, the spleen plays a crucial role in filtering and removing old or damaged platelets from the bloodstream. Platelets express adhesion molecules, such as Integrin subunit alpha 2b (ITGA2B), and the chemokines, such as (PF4).

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ITGA2B - spleen

ITGA2B
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PF4 - spleen

PF4

Macrophages

Macrophages in the spleen are diverse and play crucial roles in various functions, including blood filtration, immune response, and iron recycling. They are found in different regions of the spleen, with red pulp macrophages primarily involved in removing old or damaged red blood cells and recycling iron, while marginal zone macrophages and marginal metallophilic macrophages in the marginal zone are specialized in capturing blood-borne pathogens and initiating immune responses. Genes classified as having specificity in macrophages of the spleen include CD68 (CD68), and the lyzosomal enzyme Tripeptidyl peptidase 1 (TPP1).

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CD68 - spleen

CD68
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TPP1 - spleen

TPP1

White pulp

The white pulp of the spleen is the primary immunological region, comprising about 20-25% of splenic tissue. It consists of lymphoid follicles containing mainly B cells, surrounded by T cell-rich areas called periarteriolar lymphoid sheaths (PALS). The white pulp plays a crucial role in initiating adaptive immune responses against blood-borne antigens. It is organized around central arterioles and contains specialized antigen-presenting cells that help activate T and B lymphocytes, leading to antibody production and cell-mediated immune responses.

T-cells

T cells in the spleen are primarily located in the T cell zone (also called the periarteriolar lymphoid sheath or PALS) that surrounds the main lymphoid follicle and central arteriole. These T cells, including naive and central memory T cells, can migrate between the red pulp and white pulp, guided by chemokine gradients and specialized stromal cells, to participate in immune responses against blood-borne antigens. Genes classified as having specificity in T-cells in the spleen include CD5 (CD5), and the CD3 delta subunit (CD3D).

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CD5 - spleen

CD5
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CD3D - spleen

CD3D

B-cells

B cells in the spleen are primarily located in the white pulp, specifically in the follicles and marginal zone. Follicular B cells participate mainly in T cell-dependent immune responses, while marginal zone B cells are strategically positioned to capture blood-borne antigens and can promote both T cell-independent and T cell-dependent immune responses. Genes classified as having specificity in B-cells in the spleen include CD22 (CD22), and the signal molecule Phospholipase C gamma 2 (PLCG2).

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CD22 - spleen

CD22
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PLCG2 - spleen

PLCG2

Plasma cells

Plasma cells are specialised lymphocytes derived from B-cells that actively produce and secrete large quantities of antibodies. Genes classified as having specificity in plasma cells in the spleen include the Joining chain of multimeric IgA and IgM (JCHAIN), and the Marginal zone B and B1 cell specific protein (MZB1).

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JCHAIN - spleen

JCHAIN
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MZB1 - spleen

MZB1

Other

Hematopetic stem cells

Hematopoietic stem cells (HSCs) are present in in the spleen, though in lower numbers compared to the bone marrow. During stress conditions like anemia or inflammation, splenic HSCs can expand and contribute to extramedullary hematopoiesis, with the spleen serving as an important site for emergency blood cell production. Genes classified as having specificity in hematopetic stem cells in the spleen include cell adhesion molecule and tumour marker CEA cell adhesion molecule 6 (CEACAM6), and Membrane spanning 4-domains A3 (MS4A3), which binds to and modulates CDK2.

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CEACAM6 - spleen

CEACAM6
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MS4A3 - spleen

MS4A3

Mitotic cells

Mitotic cells in the spleen are primarily found in the white pulp, particularly in germinal centres of lymphoid follicles. These actively dividing cells are mainly B lymphocytes undergoing clonal expansion in response to antigenic stimulation, contributing to the adaptive immune response and antibody production. Genes classified as having specificity in mitotic cells in the spleen include DNA topoisomerase II alpha (TOP2A) and Kinesin family member 11 (KIF11), and Cyclin A2 (CCNA2).

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TOP2A - spleen

TOP2A
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KIF11 - spleen

KIF11
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CCNA2 - spleen

CCNA2

Smooth muscle cells

Smooth muscle cells in the spleen are primarily found in the outer capsule surrounding the spleen, as well as in the walls of blood vessels supplying the spleen with blood. These cells contribute to the contractile ability of the spleen, allowing it to adjust its size and blood content in response to physiological demands, such as during exercise or blood loss. Genes classified as having specificity in smooth muscle cells in the spleen include the filament proteins Calponin 1 (CNN1) and Desmin (DES).

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CNN1 - spleen

CNN1
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DES - spleen

DES

Fibroblasts

Fibroblasts in the spleen play crucial roles in maintaining the organ's structure and supporting immune functions. They are found in different regions of the spleen, with fibroblastic reticular cells (FRCs) predominating in the T-cell zone of the white pulp, fibroblastic dendritic cells (FDCs) in the B-cell follicles, and specialized fibroblasts in the red pulp that form a meshwork supporting blood filtration and cell trafficking. Genes classified as having specificity in fibroblasts in the spleen include Ankyrin 2 (ANK2) and the extracellular protein Fibrillin 1 (FBN1).

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ANK2 - spleen

ANK2
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FBN1 - spleen

FBN1

NK cells

NK cells are innate immune cells that play a crucial role in the body's defence against viruses, stressed cells, and tumors without requiring specific antigen recognition. They are characterized by their ability to quickly respond to threats, primarily through cytotoxic activity and cytokine production, and are found throughout the body's lymphoid tissues. Genes classified as having specificity in NK-cells in the spleen include Cathepsin W (CTSW) and Killer cell lectin like receptor C3 (KLRC3).

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CTSW - spleen

CTSW
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KLRC3 - spleen

KLRC3

Neutrophils

Neutrophils in the spleen are found in distinct populations, primarily located in the red pulp and marginal zone. These splenic neutrophils play crucial roles in blood filtration, pathogen clearance, and immune responses. Genes classified as having specificity in neutrophils in the spleen include Colony stimulating factor 3 receptor (CSF3R) and the calcium binding protein Grancalcin (GCA).

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CSF3R - spleen

CSF3R
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GCA - spleen

GCA