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 section we have 124 cell lineage enriched genes and 11 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 633 genes are cell lineage group enriched and an additional 8 genes are enhanced in this cell lineage. Altogether, 765 genes are elevated and among these 109 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 5705710 124
Group enriched 00425208 633
Lineage enhanced 6011 8
Total 630483219 765

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 57.2 541
C1QB complement C1q B chain Detected in many 140.6 85
C1QA complement C1q A chain Detected in many 226.1 60
MERTK MER proto-oncogene, tyrosine kinase Detected in single 8.6 50
PGA5 pepsinogen A5 Detected in single 4.3 44
PCDH12 protocadherin 12 Detected in single 4.6 41
C2 complement C2 Detected in single 25.9 35
ALDH1A1 aldehyde dehydrogenase 1 family member A1 Detected in many 87.3 33
AVPR2 arginine vasopressin receptor 2 Detected in single 3.6 29
SASH1 SAM and SH3 domain containing 1 Detected in single 2.6 26
CTTNBP2 cortactin binding protein 2 Detected in single 7.7 26
PGA4 pepsinogen A4 Detected in single 10.9 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 section 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, 287 genes are cell type group enriched and an additional 84 genes are enhanced in this cell type. Altogether, 381 genes are elevated and among these 61 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 45% (n=8951) of all human proteins (n=20090) are expressed in the classical monocytes and 287 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
Immune cell enriched 5320 10
Group enriched 07815059 287
Immune cell enhanced 542289 84
Total 1012318068 381

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 156.9 7
TDRD9 tudor domain containing 9 Detected in single 1.6 6
ALDH1A1 aldehyde dehydrogenase 1 family member A1 Detected in many 87.3 6
CCL8 C-C motif chemokine ligand 8 Detected in single 3.4 6
ABCC6 ATP binding cassette subfamily C member 6 Detected in single 3.4 6
NRG1 neuregulin 1 Detected in some 55.3 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 section we have 23 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 152 genes are enhanced in this cell type. Altogether, 447 genes are elevated and among these 65 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=8898) of all human proteins (n=20090) 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 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Immune cell enriched 14441 23
Group enriched 07714154 272
Immune cell enhanced 23575022 152
Total 3713819577 447

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
LYPD2 LY6/PLAUR domain containing 2 Detected in some 440.1 13
L1TD1 LINE1 type transposase domain containing 1 Detected in single 5.0 13
CKB creatine kinase B Detected in many 290.8 10
CTTNBP2 cortactin binding protein 2 Detected in single 7.7 9
VMO1 vitelline membrane outer layer 1 homolog Detected in some 111.9 9
PAQR4 progestin and adipoQ receptor family member 4 Detected in single 3.6 8
PCDH12 protocadherin 12 Detected in single 4.6 8
THAP10 THAP domain containing 10 Detected in single 4.2 7
MRAS muscle RAS oncogene homolog Detected in some 25.0 6
GSTA4 glutathione S-transferase alpha 4 Detected in many 20.0 6
ICAM4 intercellular adhesion molecule 4 (Landsteiner-Wiener blood group) Detected in many 215.4 6
PPM1N protein phosphatase, Mg2+/Mn2+ dependent 1N (putative) Detected in all 142.4 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 section we have 2 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, 301 genes are cell type group enriched and an additional 81 genes are enhanced in this cell type. Altogether, 384 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 45% (n=8965) of all human proteins (n=20090) are expressed in the intermediate monocytes and 301 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
Immune cell enriched 1100 2
Group enriched 09115456 301
Immune cell enhanced 744219 81
Total 813617565 384

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 57.2 5
KRT7 keratin 7 Detected in single 1.1 4