Granulocytes

Granulocytes are a category of white blood cells involved in the defence against bacteria and parasites. They characterized by the presence of granules in their cytoplasm that contain, e.g., defensins, lysozymes and histamines. Granulocytes are produced via granulopoiesis in the bone marrow, and the most abundant of the granulocytes is the neutrophil granulocyte, while the other types (eosinophils, basophils, and mast cells) have lower numbers.

In the Immune cell section we have 1007 cell lineage enriched genes and 59 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 640 genes are cell lineage group enriched and an additional 15 genes are enhanced in this cell lineage. Altogether, 1662 genes are elevated and among these 136 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

Figure 1. The distribution of all genes across the five specificity categories based on transcript abundance in granulocyte cell lineage as well as in the other 5 cell lineages.

Table 1. Number of genes in the subdivided categories of elevated expression in granulocyte cell lineage.

Distribution in the six cell lineages
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Lineage enriched 4330318256 1007
Group enriched 00442198 640
Lineage enhanced 11031 15
Total 4440763455 1662

Table 2. The genes with the highest level of enriched expression in granulocyte cell lineage. "nTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of granulocyte cell lineage expression to the second highest cell lineage.

Gene Description Cell lineage distribution nTPM Specificity score
CPA3 carboxypeptidase A3 Detected in single 1120.0 5543
MS4A3 membrane spanning 4-domains A3 Detected in single 2692.2 4500
PI3 peptidase inhibitor 3 Detected in single 1774.5 4390
GATA2 GATA binding protein 2 Detected in single 567.4 4016
CLC Charcot-Leyden crystal galectin Detected in all 28919.8 2255
HDC histidine decarboxylase Detected in single 686.7 2147
GATA1 GATA binding protein 1 Detected in single 463.2 1843
TCN1 transcobalamin 1 Detected in many 2379.0 1591
RHEX regulator of hemoglobinization and erythroid cell expansion Detected in single 1318.2 1550
MS4A2 membrane spanning 4-domains A2 Detected in single 275.8 1528
CXCL8 C-X-C motif chemokine ligand 8 Detected in single 439.6 1040
CA4 carbonic anhydrase 4 Detected in single 100.0 1000

Basophils

Basophils are responsible for inflammatory reactions during immune response. They have granules containing histamine, heparin, chondroitin sulfate, peroxidase and platelet-activating factor, and upon an infection they will travel from the bone marrow to the site of infection and release the granule content which will contribute to inflammation.

In the Immune cell section we have 260 basophil enriched genes and 5 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 269 genes are cell type group enriched and an additional 398 genes are enhanced in this cell type. Altogether, 927 genes are elevated and among these 49 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

Isolation of the basophils was done from whole blood. Erythrocytes were eliminated by HetaSep sedimentation method. Remaining erythrocytes, debris and cell aggregates were eliminated by gating on CD45+ cells and based on scatter profiles. The basophils were sorted as CD123+/CD193+/CD38+/CD3neg/CD11cneg/ CD15neg/CD16neg/CD20neg/CD56neg/HLA-Drneg/SSClow cells, and 2,000 – 5,800 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 44% (n=8819) of all human proteins (n=20162) are expressed in the basophils and 269 of these genes show an elevated expression in basophils compared to the other 17 cell types (see figure below).

Figure 2. The distribution of all genes across the five specificity categories based on transcript abundance in basophil cell type as well as in the other 17 cell types.

Table 3. Number of genes in the subdivided categories of elevated expression in basophils.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Immune cell enriched 136456118 260
Group enriched 010411451 269
Immune cell enhanced 839712791 398
Total 219246302160 927

Table 4. The genes with the highest level of enriched expression in basophils. "nTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of basophil cell type expression to the second highest cell type.

Gene Description Cell type distribution nTPM Specificity score
HDC histidine decarboxylase Detected in single 686.7 2147
CPA3 carboxypeptidase A3 Detected in single 1120.0 1540
MS4A3 membrane spanning 4-domains A3 Detected in some 2692.2 1476
TPSAB1 tryptase alpha/beta 1 Detected in single 90.0 900
MS4A2 membrane spanning 4-domains A2 Detected in single 275.8 873
IL4 interleukin 4 Detected in single 476.8 862
TRIM64B tripartite motif containing 64B Detected in single 83.9 839
GCSAML germinal center associated signaling and motility like Detected in single 228.8 670
TEX101 testis expressed 101 Detected in single 55.7 557
CD200R1L CD200 receptor 1 like Detected in single 85.4 386
SLC45A3 solute carrier family 45 member 3 Detected in single 40.6 382
GATA2 GATA binding protein 2 Detected in some 567.4 361

Eosinophils

Eosinophils mainly function in defence against multicellular parasites, but they also function as antigen-presenting cells and can participate in phagocytosis. They fight parasites by releasing the toxic chemical mediators, including eosinophil peroxidase, lipase, major basic protein, RNase and DNase, contained in their granules.

In the Immune cell section we have 74 eosinophil enriched genes and 3 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 289 genes are cell type group enriched and an additional 209 genes are enhanced in this cell type. Altogether, 572 genes are elevated and among these 57 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The eosinophils were isolated from whole blood. Erythrocytes were eliminated by the HetaSep sedimentation method. Remaining erythrocytes, debris and cell aggregates were eliminated by gating on CD45+ events and based on scatter profile. The eosinophils were sorted as CD193+/CD15low/CD16low/HLA-Drlow/SSChigh cells and 8,000 – 30,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing.The transcriptome analysis shows that 43% (n=8701) of all human proteins (n=20162) are expressed in the eosinophils and 289 of these genes show an elevated expression in eosinophils compared to the other 17 cell types (see figure below).

Figure 3. The distribution of all genes across the five specificity categories based on transcript abundance in eosinophil cell type as well as in the other 17 cell types.

Table 5. Number of genes in the subdivided categories of elevated expression in esinophils.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Immune cell enriched 3216215 74
Group enriched 09513460 289
Immune cell enhanced 27558542 209
Total 59166240107 572

Table 6. The genes with the highest level of enriched expression in esinophils. "nTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of eosinophil expression to the second highest cell type.

Gene Description Cell type distribution nTPM Specificity score
CEBPE CCAAT enhancer binding protein epsilon Detected in some 504.5 271
SEMG1 semenogelin 1 Detected in single 26.9 239
ALOX15 arachidonate 15-lipoxygenase Detected in some 608.0 194
CCL23 C-C motif chemokine ligand 23 Detected in some 184.4 163
PRSS41 serine protease 41 Detected in single 10.5 106
LRRC17 leucine rich repeat containing 17 Detected in single 9.9 94
PRSS33 serine protease 33 Detected in some 1353.2 68
THBS4 thrombospondin 4 Detected in single 4.6 46
TMIGD3 transmembrane and immunoglobulin domain containing 3 Detected in some 63.0 44
ADORA3 adenosine A3 receptor Detected in many 602.8 40
SIGLEC8 sialic acid binding Ig like lectin 8 Detected in some 290.9 38
MYCT1 MYC target 1 Detected in single 30.7 33

Neutrophils

Neutrophils 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.

In the Immune cell section we have 235 neutrophil enriched genes and 27 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 330 genes are cell type group enriched and an additional 469 genes are enhanced in this cell type. Altogether, 1034 genes are elevated and among these 114 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The neutrophils were isolated from whole blood. Erythrocytes were eliminated by the HetaSep sedimentation method. Remaining erythrocytes, debris and cell aggregates were eliminated by gating on CD45+ events and scatter profiles. The neutrophils were sorted as CD15+/CD16+/SSChigh cells, and 50,000 – 190,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 43% (n=8599) of all human proteins (n=20162) are expressed in the neutrophils and 330 of these genes show an elevated expression in neutrophils compared to the other 17 cell types (see figure below).

Figure 4. The distribution of all genes across the five specificity categories based on transcript abundance in neutrophil cell type as well as in the other 17 cell types.

Table 7. Number of genes in the subdivided categories of elevated expression in neutrophils.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Immune cell enriched 77576635 235
Group enriched 010815171 330
Immune cell enhanced 7080168151 469
Total 147245385257 1034

Table 8. The genes with the highest level of enriched expression in neutrophils. "nTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of neutrophil cell expression to the second highest cell type.

Gene Description Cell type distribution nTPM Specificity score
PI3 peptidase inhibitor 3 Detected in some 1774.5 1026
CHI3L1 chitinase 3 like 1 Detected in single 472.1 494
CXCL8 C-X-C motif chemokine ligand 8 Detected in some 439.6 408
FCGR3B Fc gamma receptor IIIb Detected in many 6077.6 356
ANXA3 annexin A3 Detected in single 208.7 328
TGM3 transglutaminase 3 Detected in single 30.4 295
CXCL1 C-X-C motif chemokine ligand 1 Detected in single 47.5 244
BTNL3 butyrophilin like 3 Detected in single 22.4 207
C4BPA complement component 4 binding protein alpha Detected in single 29.6 137
MMP9 matrix metallopeptidase 9 Detected in some 272.9 127
MME membrane metalloendopeptidase Detected in some 139.9 123
CXCL6 C-X-C motif chemokine ligand 6 Detected in single 10.4 105