Immunity Feng Jue et al. used clonal lineage tracing to reveal the common origin of traditional dendritic cells and plasmacytoid dendritic cells

Editor | Xi Continuous differentiation of hematopoietic stem cells in the adult bone marrow maintains the homeostasis of the entire adult immune system
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Understanding hematopoiesis and homeostasis in other adult tissues requires precise delineation of differentiation trajectories from stem cells to mature cells at single-cell resolution
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Clonal relationships between mature hematopoietic lineages have been explored using DNA barcodes during embryogenesis or transplantation, however specific clonal labeling and tracking of adult hematopoietic stem or progenitor cells warrants continued research
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Dendritic cells (DCs) are key sentinel cells of the immune system
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Such cells detect pathogens and coordinate innate and adaptive immune responses through pattern recognition receptors
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Traditional or classical dendritic cells are divided into two main types, cDC1 and cDC2, according to different functional properties and genetic requirements, which can efficiently present antigens to T lymphocytes
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Another class of plasmacytoid dendritic cells (pDCs) are specialized for the detection of pathogen-derived nucleic acids and secretion of type I interferons (IFN-I), key mediators of antiviral immune responses
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All dendritic cells in peripheral lymphoid organs such as the spleen are relatively short-lived and their development is driven by the cytokine Flt3 ligand (Flt3L) through its receptor Flt3 signaling pathway
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Dendritic cells are considered a branch distinct from myeloid cells and share an upstream progenitor (monocyte-DC progenitor or MDP) with monocytes 
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All DC subsets develop from a common progenitor (common DC progenitor or CDP)
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pDCs are fully differentiated in the bone marrow, whereas all DC precursors (pre-DCs) and committed cDC1 or cDC2 precursors (pre-DC1 or pre-DC2) differentiation begin in the bone marrow and undergo terminal differentiation in the periphery
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However, these precursor cells were initially identified following transplantation, and their in vivo identity and differentiation profile were unclear
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In addition, it has recently been suggested that pDCs develop primarily from lymphoid progenitors and are therefore distinct in origin from cDC progenitors
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Finally, the application of clone-level DNA barcoding to transplantation of murine progenitors and single-cell culture of human progenitors suggests that the fate of individual DC subsets may already be determined in hematopoietic stem cells or early pluripotent progenitors (MPPs)
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Therefore, clonal resolution in unmanipulated animals to elucidate the origin of DC subtype development and the hierarchical types of committed lineages is a very interesting study
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On February 17, 2022, the team of Boris Reizis and Feng Jue of NYU Grossman School of Medicine published an article on Immunity.
Clonal lineage tracing reveals shared origin of conventional and plasmacytoid dendritic cells.
and common origin of plasmacytoid dendritic cells
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We established an inducible clonal cell barcoding system (FlipJump) and combined it with a single-cell transcriptome-immunophenotyping sequencing system (CITE-seq) for lineage tracing of hematopoietic stem and DC progenitors.
research
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Induction tracing of Cx3cr1+ hematopoietic progenitor cells in bone marrow indicated that subpopulations of Cx3cr1+ hematopoietic progenitor cells in bone marrow can simultaneously generate DCs including pDC, cDC1 and cDC2
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Clonal profiling of hematopoietic stem cells (HSCs) and Cx3cr1+ progenitor cells revealed clonal sharing between cDC1 and pDCs, but not between the two cDC subpopulations or between pDCs and B cells
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This coupled with CITE-Seq analysis of differentiated hematopoietic stem cells and Cx3cr1+ progenitors identified progressive stages of pDC development including Cx3cr1+ Ly-6D+ pro-pDCs distinct from lymphoid progenitors
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These results reveal the common origin of pDCs and DCs and propose a revised scheme for the shared clonal relationship between pDCs and DC1
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Link to the original text: https://doi.
org/10.
1016/j.
immuni.
2022.
01.
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