Decoding the Heterogeneity of Human Dendritic Cell Subsets

ScRNA-seq analyses of human DC subsets have revealed unexpected heterogeneity within cDC2 and pDC subsets, leading to the identification of new populations. AXL+SIGLEC6+ DCs display a mixed pDC/cDC transcriptional profile and can differentiate into cDC2 when placed in culture. DC3 have a mixed cDC2/monocyte gene expression profile and develop from precursors distinct from other DC lineages and monocytes. All human DC subsets express a convergent transcriptional program when they mature in vivo, in lymphoid organs or peripheral tissues. In the ontogeny-based classification of human DCs, DC3 may represent a new DC subset, along with pDC, cDC1, cDC2, and mo-DC. Dendritic cells (DCs) have been classified into distinct subsets based on phenotype and ontogeny. In the past few years, high throughput single-cell approaches have revealed further heterogeneity of human DCs, in particular at the transcriptomic level. Herein examined, are recent studies describing new human DC populations based on single-cell RNA-seq analysis, and a unified view of these emerging DC populations is presented. Also assessed are the features that define bona fide DC lineages, as opposed to cell states of the same lineage. Finally, where these newly described DC populations fit in the ontogeny-based classification of human DCs is examined. Dendritic cells (DCs) have been classified into distinct subsets based on phenotype and ontogeny. In the past few years, high throughput single-cell approaches have revealed further heterogeneity of human DCs, in particular at the transcriptomic level. Herein examined, are recent studies describing new human DC populations based on single-cell RNA-seq analysis, and a unified view of these emerging DC populations is presented. Also assessed are the features that define bona fide DC lineages, as opposed to cell states of the same lineage. Finally, where these newly described DC populations fit in the ontogeny-based classification of human DCs is examined. abnormal infiltration of fluid in the abdomen. next generation sequencing method providing the DNA sequences of open chromatin regions; this allows the inference of regions that are accessible for transcription factor binding. immune cell specialized for antigen presentation and T cell stimulation; can migrate from peripheral tissues to lymphoid organs. method to trace cell lineages, for instance by transferring purified precursor cells or inserting a genetic mark such as a fluorochrome in precursor cells. mucosal connective tissue that lies between the epithelium and underlying tissues. antigen presenting immune cell residing in peripheral and lymphoid tissues, and specialized in ingesting pathogens and dying cells. process by which dendritic cells modify their morphology and expression of molecules (including surface), rendering the cells more efficient in their interaction with T cells. immune cell that circulates in the blood and massively infiltrates tissues upon inflammation. rare genetic disorder due to the loss of function of the transcription factor 4 (TCF4), characterized by a moderate to severe intellectual disability. Patients show an impairment of the pDC compartment in terms of number, phenotype, and function. next generation sequencing method, providing RNA expression profiles from individual cells. population of DCs displaying an intermediate phenotype between cDC and pDC. (in single-cell RNAseq) grouping of a set of cells that are more similar to each other than to other groups of cells, based on their expression data. Unbiased clustering (also termed unsupervised clustering) is performed without consideration of prior knowledge about the cell attributes. Common clustering methods include hierarchical clustering, graph-based clustering, and k-means clustering.