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 Immune cell resource we have 132 cell lineage enriched genes and 14 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 620 genes are cell lineage group enriched and an additional 6 genes are enhanced in this cell lineage. Altogether, 758 genes are elevated and among these 108 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 6105714 132
Group enriched 00417203 620
Lineage enhanced 4011 6
Total 650475218 758

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

Gene
Description
Cell lineage distribution
nTPM
Specificity score
C1QC complement C1q C chain Detected in single 56.5 559
C1QB complement C1q B chain Detected in many 142.5 83
C1QA complement C1q A chain Detected in many 227.9 59
MERTK MER proto-oncogene, tyrosine kinase Detected in single 8.7 50
ENSG00000289692 novel protein Detected in single 10.7 48
PGA5 pepsinogen A5 Detected in single 4.3 44
PCDH12 protocadherin 12 Detected in single 4.7 41
ALDH1A1 aldehyde dehydrogenase 1 family member A1 Detected in many 87.5 33
C2 complement C2 Detected in single 26.1 33
AVPR2 arginine vasopressin receptor 2 Detected in single 3.5 30
PGA4 pepsinogen A4 Detected in single 10.8 26
CTTNBP2 cortactin binding protein 2 Detected in single 7.9 26

Classical monocytes

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

In the Immune cell resource we have 10 classical monocyte enriched genes and 0 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 285 genes are cell type group enriched and an additional 80 genes are enhanced in this cell type. Altogether, 375 genes are elevated and among these 59 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 44% (n=8903) of all human proteins (n=20162) are expressed in the classical monocytes and 285 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 19 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Immune cell enriched 5320 10
Group enriched 07914759 285
Immune cell enhanced 737279 80
Total 1211917668 375

Table 4. The genes with the highest level of enriched expression in classical monocyte cells. "nTPM" 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
nTPM
Specificity score
S1PR3 sphingosine-1-phosphate receptor 3 Detected in single 7.0 18
RXFP2 relaxin family peptide receptor 2 Detected in single 1.7 10
CLEC5A C-type lectin domain containing 5A Detected in some 9.1 8
CYP1B1 cytochrome P450 family 1 subfamily B member 1 Detected in many 157.2 7
TDRD9 tudor domain containing 9 Detected in single 1.5 6
ALDH1A1 aldehyde dehydrogenase 1 family member A1 Detected in many 87.5 6
CCL8 C-C motif chemokine ligand 8 Detected in single 3.4 6
NRG1 neuregulin 1 Detected in some 53.9 5
ABCC6 ATP binding cassette subfamily C member 6 Detected in single 3.9 5
FXYD6 FXYD domain containing ion transport regulator 6 Detected in some 37.7 4

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 Immune cell resource we have 24 non-classical monocyte enriched genes and 0 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 272 genes are cell type group enriched and an additional 157 genes are enhanced in this cell type. Altogether, 453 genes are elevated and among these 68 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 44% (n=8861) of all human proteins (n=20162) are expressed in the non-classical monocytes and 272 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 19 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Immune cell enriched 14541 24
Group enriched 08013854 272
Immune cell enhanced 25575322 157
Total 3914219577 453

Table 6. The genes with the highest level of enriched expression in non-classical monocyte cells. "nTPM" 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
nTPM
Specificity score
L1TD1 LINE1 type transposase domain containing 1 Detected in single 5.1 13
LYPD2 LY6/PLAUR domain containing 2 Detected in some 442.4 13
CKB creatine kinase B Detected in many 292.6 10
CTTNBP2 cortactin binding protein 2 Detected in single 7.9 9
VMO1 vitelline membrane outer layer 1 homolog Detected in some 112.2 9
PAQR4 progestin and adipoQ receptor family member 4 Detected in single 3.6 8
PCDH12 protocadherin 12 Detected in single 4.7 8
THAP10 THAP domain containing 10 Detected in single 4.2 7
MRAS muscle RAS oncogene homolog Detected in some 25.3 6
GSTA4 glutathione S-transferase alpha 4 Detected in many 20.1 6
ICAM4 intercellular adhesion molecule 4 (Landsteiner-Wiener blood group) Detected in many 216.1 6
PPM1N protein phosphatase, Mg2+/Mn2+ dependent 1N (putative) Detected in all 137.2 6

Intermediate monocytes

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

In the Immune cell resource we have 1 intermediate 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, 300 genes are cell type group enriched and an additional 80 genes are enhanced in this cell type. Altogether, 381 genes are elevated and among these 71 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 44% (n=8907) of all human proteins (n=20162) are expressed in the intermediate monocytes and 300 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 19 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Immune cell enriched 0100 1
Group enriched 09514956 300
Immune cell enhanced 643229 80
Total 613917165 381

Table 8. The genes with the highest level of enriched expression in intermediate monocyte cell. "nTPM" 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
nTPM
Specificity score
C1QC complement C1q C chain Detected in some 56.5 6