Monocytes

Monocytes are the largest type of leukocyte and are involved in immune responses to bacteria, viruses, and fungi. They can differentiate both into macrophages that can penetrate into tissues and perform defense functions, or into myeloid lineage dendritic cells to effect an immune response. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.

In the Blood Atlas we have 189 cell lineage 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, 762 genes are cell lineage group enriched and an additional 11 genes are enhanced in this cell lineage. Altogether, 962 genes are elevated and among these 213 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 monocyte celll lineage as well as in the other 5 cell lineages

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

Distribution in the six cell lineages
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Lineage enriched 1120707 189
Group enriched 00641121 762
Lineage enhanced 9020 11
Total 1210713128 962

Table 2. The genes with the highest level of enriched expression in monocyte 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 monocyte cell lineage expression to the second highest cell lineage.

Gene Description Cell lineage distribution pTPM Specificity score
C1QC complement C1q C chain Detected in single 58.7 284
C1QB complement C1q B chain Detected in single 147.4 83
PGA5 pepsinogen 5, group I (pepsinogen A) Detected in single 4.9 77
C1QA complement C1q A chain Detected in single 221.5 57
MERTK MER proto-oncogene, tyrosine kinase Detected in single 8.8 48
ARHGAP29 Rho GTPase activating protein 29 Detected in single 1.3 38
PALM paralemmin Detected in single 1.7 35
PCDH12 protocadherin 12 Detected in single 3.8 35
SASH1 SAM and SH3 domain containing 1 Detected in single 2.6 32
PTX4 pentraxin 4 Detected in single 0.7 31
ALDH1A1 aldehyde dehydrogenase 1 family member A1 Detected in many 84.6 30
AVPR2 arginine vasopressin receptor 2 Detected in single 3.6 28

Classical monocytes

The classical monocyte is characterized by high level expression of the CD14 cell surface receptor (CD14++ CD16− monocyte).

In the Blood Atlas we have 18 classical monocyte enriched genes and 1 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 353 genes are cell type group enriched and an additional 125 genes are enhanced in this cell type. Altogether, 496 genes are elevated and among these 104 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The classical monocytes were isolated from PBMCs. Debris, cell aggregates and most of lymphocytes were eliminated based on scatter profiles. The remaining NK, T- and B-cells were eliminated by selecting CD3neg/CD19neg/CD20neg/CD56neg cells. The classical monocytes were sorted as CD14+/CD16neg cells and 50,000 – 190,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 52% (n=10180) of all human proteins (n=19,670) are expressed in the classical monocytes and 353 of these genes show an elevated expression in classical monocytes 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 classical monocyte cells as well as in the other 17 cell types.

Table 3. Number of genes in the subdivided categories of elevated expression in classical monocyte cells.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 12600 18
Group enriched 015617324 353
Cell type enhanced 1860443 125
Total 3022221727 496

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

Gene Description Cell type distribution pTPM Specificity score
S1PR3 sphingosine-1-phosphate receptor 3 Detected in single 6.8 17
CCL13 C-C motif chemokine ligand 13 Detected in single 0.1 14
PTGFR prostaglandin F receptor Detected in single 0.1 13
CCL7 C-C motif chemokine ligand 7 Detected in single 0.1 12
RXFP2 relaxin/insulin like family peptide receptor 2 Detected in single 1.7 11
LGI2 leucine rich repeat LGI family member 2 Detected in single 0.1 10
SPATA12 spermatogenesis associated 12 Detected in single 0.0 10
CCL8 C-C motif chemokine ligand 8 Detected in single 2.3 8
CLEC5A C-type lectin domain containing 5A Detected in some 9.4 8
TRPV4 transient receptor potential cation channel subfamily V member 4 Detected in single 0.6 7
CYP1B1 cytochrome P450 family 1 subfamily B member 1 Detected in some 148.2 6
ADAMTS5 ADAM metallopeptidase with thrombospondin type 1 motif 5 Detected in single 0.1 6

Non-classical monocytes

The non-classical monocyte shows low level expression of CD14 and additional co-expression of the CD16 receptor (CD14+CD16++ monocyte).

In the Blood Atlas we have 35 non-classical monocyte enriched genes and 2 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 300 genes are cell type group enriched and an additional 163 genes are enhanced in this cell type. Altogether, 498 genes are elevated and among these 108 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The non-classical monocytes were isolated from PBMCs. Debris, cell aggregates and most of lymphocytes were eliminated based on scatter profiles. The remaining NK, T- and B-cells were eliminated by selecting CD3neg/CD19neg/CD20neg/CD56neg cells. The non-classical monocytes were sorted as CD14low/CD16+ cells and 1,000 – 26,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 49% (n=9720) of all human proteins (n=19,670) are expressed in the non-classical monocytes and 300 of these genes show an elevated expression in non-classical monocytes 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 non-classical monocyte cells as well as in the other 17 cell types.

Table 5. Number of genes in the subdivided categories of elevated expression in non-classical monocyte cells.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 211130 35
Group enriched 012615123 300
Cell type enhanced 1660825 163
Total 3719723628 498

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

Gene Description Cell type distribution pTPM Specificity score
PLPPR4 phospholipid phosphatase related 4 Detected in single 0.3 22
SYTL5 synaptotagmin like 5 Detected in single 0.2 19
TNFSF18 TNF superfamily member 18 Detected in single 0.2 19
PRTG protogenin Detected in single 0.2 18
CABP4 calcium binding protein 4 Detected in single 12.0 13
LYPD2 LY6/PLAUR domain containing 2 Detected in some 451.7 13
EPO erythropoietin Detected in single 0.1 13
KRT78 keratin 78 Detected in single 0.0 11
L1TD1 LINE1 type transposase domain containing 1 Detected in single 5.1 11
CKB creatine kinase B Detected in some 192.5 10
VMO1 vitelline membrane outer layer 1 homolog Detected in some 111.3 9
DCSTAMP dendrocyte expressed seven transmembrane protein Detected in single 0.2 8

Intermediate monocytes

The intermediate monocyte has high level expression of CD14 and low level expression of CD16 (CD14++CD16+ monocytes).

In the Blood Atlas we have 15 intermediate monocyte enriched genes and 4 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 360 genes are cell type group enriched and an additional 142 genes are enhanced in this cell type. Altogether, 517 genes are elevated and among these 117 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The intermediate monocytes were isolated from PBMCs. Debris, cell aggregates and most of lymphocytes were eliminated based on scatter profiles. The remaining NK, T- and B-cells were eliminated by selecting CD3neg/CD19neg/CD20neg/CD56neg cells. The intermediate monocytes were sorted as CD14+/CD16+ cells and 2,000 – 5,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 51% (n=9980) of all human proteins (n=19,670) are expressed in the intermediate monocytes and 360 of these genes show an elevated expression in intermediate monocytes 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 intermediate monocyte cells as well as in the other 17 cell types.

Table 7. Number of genes in the subdivided categories of elevated expression in intermediate monocyte cell.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Cell type enriched 14100 15
Group enriched 016916724 360
Cell type enhanced 1876462 142
Total 3224621326 517

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

Gene Description Cell type distribution pTPM Specificity score
CCL26 C-C motif chemokine ligand 26 Detected in single 0.5 27
SORCS1 sortilin related VPS10 domain containing receptor 1 Detected in single 0.4 24
GUCA2B guanylate cyclase activator 2B Detected in single 0.2 19
GAL galanin and GMAP prepropeptide Detected in single 0.1 15
MYBPC1 myosin binding protein C, slow type Detected in single 0.1 14
IFNE interferon epsilon Detected in single 0.0 10
PGC progastricsin Detected in single 0.2 7
KEL Kell blood group, metallo-endopeptidase Detected in single 0.1 7
CXCL12 C-X-C motif chemokine ligand 12 Detected in single 0.4 6
C1QC complement C1q C chain Detected in some 58.7 6
MS4A6E membrane spanning 4-domains A6E Detected in single 0.1 5
RSPO2 R-spondin 2 Detected in single 0.2 5