A rule-based data-informed cellular consensus map of the human mononuclear phagocyte cell space

Abstract

Highlights  Defining a consensus of the human myeloid cell compartment in peripheral blood  3 monocytes subsets, pDC, cDC1, DC2, DC3 and precursor DC make up the compartment  Distinguish myeloid cell compartment from other cell spaces, e.g. the NK cell space 5  Providing a generalizable method for building consensus maps for the life sciences 4 Abstract Single-cell genomic techniques are opening new avenues to understand the basic units of life.Large international efforts, such as those to derive a Human Cell Atlas, are driving progress in this area; here, cellular map generation is key. To expedite the inevitable iterations of these underlying maps, we have developed a rule-based data-informed approach to build next 5 generation cellular consensus maps. Using the human dendritic-cell and monocyte compartment in peripheral blood as an example, we performed computational integration of previous, partially overlapping maps using an approach we termed 'backmapping', combined with multi-color flowcytometry and index sorting-based single-cell RNA-sequencing. Our general strategy can be applied to any atlas generation for humans and other species. 10

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

“…Nevertheless, the frequency of these cells is very low and supplementary studies are needed to fully understand their biological relevance. Moreover, two recent studies showed that one of these four subsets was a contamination by NK cells (92,93).…”

Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases

“…With the development of multi-dimensional single-cell techniques, assessment at the single-cell transcriptome level unexpectedly suggested 4 monocyte subsets in healthy volunteers; classical, non-classical, and 2 monocyte subsets, one expressing genes involved in cell cycle, differentiation and trafficking and the other being associated with a NK cell-like signature (15). By generating new single-cell transcriptomics data we now have evidence that the latter monocyte subset was due to misclassification of a particular subset of NK cells, indicating that the current model with 3 major subsets is still valid (16).…”

“…Finally, a role for the SLAN + subset of non-classical monocytes in TNF overproduction in viraemic HIV-infected patients was proposed, suggesting that they might be considered as a major actor in the immune hyperactivation of the disease (41). While SLAN seems to delineate a subset of non-classical monocytes, there is no evidence for transcriptional differences between SLAN + and SLAN − cells (16) which requires further work to understand the reasons for the discrepancy between homogeneity at the transcriptional, but heterogeneity at the protein level.…”

Mind the Map: Technology Shapes the Myeloid Cell Space

“…More recently, by combining index sorting and high-content single-cell RNA-sequencing, we show further evidence that Slan expression does not reflect different cell subsets as the underlying overall transcriptional program is not different between Slan high and Slan low cells. Moreover, we clearly show that Slan+ cells are all non-classical monocytes (125).…”

“…We defined cell types and subsets by a combination of function, phenotype and transcriptional profile, which lead to the identification of precursors (pre-cDCs) for the cDC1 and cDC2 subsets in addition to the three main DC subsets (5). To reconcile these two major initial reports, we developed a strategy that allows developing cell type classification consensus based on phenotypic and transcriptional features also including prior knowledge (125). This approach revealed that (1) the AXL + Siglec6 + DCs (AS-DCs) described by Villani et al are mainly pre-cDCs as described in (5), (2) Mono4 are contaminating CD56 dim NK cells, and (3) cells introduced as CD16 + CSF1-R + CTSS + DCs are not belonging to the DC lineage.…”