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 Blood Atlas we have 1160 cell lineage enriched genes and 273 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 795 genes are cell lineage group enriched and an additional 35 genes are enhanced in this cell lineage. Altogether, 1990 genes are elevated and among these 448 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 5940382184 1160
Group enriched 00674121 795
Lineage enhanced 32030 35
Total 62601059305 1990

Table 2. The genes with the highest level of enriched expression in granulocyte cell lineage. "pTPM" 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 pTPM Specificity score
CLC Charcot-Leyden crystal galectin Detected in single 26187.2 1987
MS4A3 membrane spanning 4-domains A3 Detected in single 3204.5 1963
PI3 peptidase inhibitor 3 Detected in single 1498.5 1571
TCN1 transcobalamin 1 Detected in single 1938.0 1202
CPA3 carboxypeptidase A3 Detected in single 1037.0 1118
HDC histidine decarboxylase Detected in single 582.1 835
GATA2 GATA binding protein 2 Detected in single 550.8 813
CXCL8 C-X-C motif chemokine ligand 8 Detected in single 381.0 794
GATA1 GATA binding protein 1 Detected in single 472.8 784
MS4A2 membrane spanning 4-domains A2 Detected in single 432.9 720
IL4 interleukin 4 Detected in single 455.7 679
SIGLEC8 sialic acid binding Ig like lectin 8 Detected in single 305.3 623

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 Blood Atlas we have 225 basophil enriched genes and 41 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 301 genes are cell type group enriched and an additional 400 genes are enhanced in this cell type. Altogether, 926 genes are elevated and among these 187 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 50% (n=9881) of all human proteins (n=19,670) are expressed in the basophils and 301 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
Cell type enriched 14148297 225
Group enriched 016910824 301
Cell type enhanced 6214915732 400
Total 20336629463 926

Table 4. The genes with the highest level of enriched expression in basophils. "pTPM" 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 pTPM Specificity score
CPA3 carboxypeptidase A3 Detected in single 1037.0 1118
MS4A3 membrane spanning 4-domains A3 Detected in single 3204.5 1061
HDC histidine decarboxylase Detected in single 582.1 835
MS4A2 membrane spanning 4-domains A2 Detected in single 432.9 720
IL4 interleukin 4 Detected in single 455.7 679
GCSAML germinal center associated signaling and motility like Detected in single 194.1 439
GATA2 GATA binding protein 2 Detected in single 550.8 339
TPSAB1 tryptase alpha/beta 1 Detected in single 78.1 308
CD200R1L CD200 receptor 1 like Detected in single 81.3 304
TEX101 testis expressed 101 Detected in single 50.4 246
SLC45A3 solute carrier family 45 member 3 Detected in single 42.6 226
TRIM64B tripartite motif containing 64B Detected in single 41.9 223

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 Blood Atlas we have 106 eosinophil enriched genes and 26 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 321 genes are cell type group enriched and an additional 252 genes are enhanced in this cell type. Altogether, 679 genes are elevated and among these 161 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 49% (n=9608) of all human proteins (n=19,670) are expressed in the eosinophils and 321 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
Cell type enriched 5724232 106
Group enriched 015113931 321
Cell type enhanced 327412323 252
Total 8924928556 679

Table 6. The genes with the highest level of enriched expression in esinophils. "pTPM" 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 pTPM Specificity score
CEBPE CCAAT/enhancer binding protein epsilon Detected in single 581.4 201
SEMG1 semenogelin I Detected in single 28.5 192
ALOX15 arachidonate 15-lipoxygenase Detected in single 620.6 183
CCL23 C-C motif chemokine ligand 23 Detected in single 194.6 173
PRSS41 serine protease 41 Detected in single 10.3 116
PRSS33 serine protease 33 Detected in some 1352.0 78
THBS4 thrombospondin 4 Detected in single 4.9 51
FOXI1 forkhead box I1 Detected in single 1.7 48
SIGLEC8 sialic acid binding Ig like lectin 8 Detected in some 305.3 42
SVOPL SVOP like Detected in single 1.2 41
EPX eosinophil peroxidase Detected in single 2.3 41
FAM170B family with sequence similarity 170 member B Detected in single 2.1 40

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 Blood Atlas we have 355 neutrophil enriched genes and 87 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 391 genes are cell type group enriched and an additional 715 genes are enhanced in this cell type. Altogether, 1461 genes are elevated and among these 347 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 52% (n=10179) of all human proteins (n=19,670) are expressed in the neutrophils and 391 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
Cell type enriched 158918422 355
Group enriched 020015734 391
Cell type enhanced 139212235129 715
Total 297503476185 1461

Table 8. The genes with the highest level of enriched expression in neutrophils. "pTPM" 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 pTPM Specificity score
PI3 peptidase inhibitor 3 Detected in single 1498.5 1121
CHI3L1 chitinase 3 like 1 Detected in single 399.5 490
CXCL8 C-X-C motif chemokine ligand 8 Detected in single 381.0 428
ANXA3 annexin A3 Detected in single 159.4 319
CXCL1 C-X-C motif chemokine ligand 1 Detected in single 38.7 253
TGM3 transglutaminase 3 Detected in single 25.3 205
BTNL3 butyrophilin like 3 Detected in single 19.1 178
C4BPA complement component 4 binding protein alpha Detected in single 28.2 153
MMP9 matrix metallopeptidase 9 Detected in single 241.4 141
MME membrane metalloendopeptidase Detected in single 225.7 129
AC106774.10 Detected in single 9.0 122
OTX1 orthodenticle homeobox 1 Detected in single 7.7 113