Abstract
SummaryConventional dendritic cells (cDCs) are thought to descend from a DC precursor downstream of the common myeloid progenitor (CMP). However, a mouse lymphoid-primed multipotent progenitor has been shown to generate cDCs following a DC-specific developmental pathway independent of monocyte and granulocyte poiesis. Similarly, here we show that, in humans, a large fraction of multipotent lymphoid early progenitors (MLPs) gives rise to cDCs, in particular the subset known as cDC1, identified by co-expression of DNGR-1 (CLEC9A) and CD141 (BDCA-3). Single-cell analysis indicates that over one-third of MLPs have the potential to efficiently generate cDCs. cDC1s generated from CMPs or MLPs do not exhibit differences in transcriptome or phenotype. These results demonstrate an early imprinting of the cDC lineage in human hematopoiesis and highlight the plasticity of developmental pathways giving rise to human DCs.
Highlights
Dendritic cells (DCs) are mononuclear phagocytes crucial for the initiation and regulation of immune responses (Steinman et al, 2003)
To analyze the actual origin of DCs developing in FSG4 cultures, we isolated different hematopoietic progenitors from human cord blood by flow cytometry (Figure 1A) following established protocols (Akashi et al, 2000; Chicha et al, 2004; Doulatov et al, 2010) to sort multipotent lymphoid early progenitors (MLPs), common myeloid progenitor (CMP), and granulocyte/macrophage progenitors (GMPs), which originate from CMPs but are known to overlap in phenotype with DC precursors (Lee et al, 2015)
Sorted MLP, CMP, and GMP populations were cultured with FSG4, and their DC- and monocyte/macrophage-generating potential was analyzed
Summary
Dendritic cells (DCs) are mononuclear phagocytes crucial for the initiation and regulation of immune responses (Steinman et al, 2003). They are classically divided into plasmacytoid DCs (pDCs) and two distinct subsets of conventional DCs (cDCs), termed cDC1 and cDC2 (Guilliams et al, 2014). Mouse CD11b+ cDC2s are considerably heterogeneous and include a subtype whose differentiation depends on KLF4 and induces Th2-dominated immunity (Tussiwand et al, 2015) as well as gut CD103+CD11b+ DCs that prominently induce Th17 responses against pathobionts (Persson et al, 2013; Schlitzer et al, 2013). Additional DC subtypes have very recently been described in human blood, suggesting that DC heterogeneity may be even greater than previously appreciated (Villani et al, 2017)
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