ScRNA-Seq to study the impact of HIV-1 on pre-DC biology [PreDC_Single_Cell_Exp1]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE201327 | GEO | 2023/01/13
REPOSITORIES: GEO
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Project description:Pre-DC have been initially described through their ontogeny. Our lab reported for the first time a pre-DC functional specificity in the context of HV-1 capture, infection and in vitro transmission as a consequence of their constitutive expression of Siglec-1. However, pre-DC immune response to viral exposure remained to be studied. This study aim to decipher innate immune response of pre-DC and cDC2 when exposed to HIV-1 in the presence or not of Vpx.
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Project description:Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. Important questions on the origins and differentiation paths of human DC populations remain elusive. Here we combined two high-dimensional technologies, single-cell mRNA sequencing and mass cytometry to define and characterize CD33+CD45RA+ DC precursors (pre-DC) present in human blood. In this study, we showed that a previously understimated pre-DC population shares surface markers with plasmacytoid DC (pDC), but has distinct functional properties that were previously attributed to pDC. Finally, we trace the origin of DCs from BM to peripheral blood and reveal that pre-DC comprise three sub-populations - 1 uncommitted sub-population and 2 lineage-committed sub-populations. The discovery of committed pre-DC populations in present in human peripheral blood confirms the existence of DC as a distinct hematopoietic lineage and opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting.
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Project description:Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally-specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here we combine two high-dimensional technologies — single-cell mRNA sequencing and Cytometry by Time-of-Flight (CyTOF), to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed sub-populations including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting.
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Project description:Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally-specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here we combine two high-dimensional technologies — single-cell mRNA sequencing and Cytometry by Time-of-Flight (CyTOF), to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed sub-populations including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting.
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Project description:Dendritic cells (DCs) are antigen sensing and presenting cells that are essential for effective immunity. Existing as a multi-subset population, divided by distinct developmental and functional characteristics1,2, DC subsets play important and unique roles in responses to pathogens, vaccines and cancer therapies, as well as during immune-pathologies. Therefore therapeutic manipulation of the DC compartment is an attractive strategy. However, our incomplete knowledge of the inter-relationship between DC subsets and how they develop from progenitors in the bone marrow (BM) has so far limited the realization of their therapeutic potential. DCs arise from a cascade of progenitors that gradually differentiate in the BM; first, the macrophage DC progenitor (MDP), then common DC progenitor (CDP), and lastly the Pre-DC, which will leave the BM to seed peripheral tissues before differentiating into mature DCs3,4. While the basic outline of this process is known, how subset commitment and development is regulated at the molecular level remains poorly understood. Here we reveal that the Pre-DC population in mice is heterogeneous, containing uncommitted Ly6c+/-Siglec-H+ cells as well as Ly6c+Siglec-H- and Ly6c-Siglec-H- sub-populations that are developmentally fated to become Th2/17-inducing CD11b+ DCs and Th1-inducing CD8α+ DCs, respectively. Using single cell analysis by microfluidic RNA sequencing, we found that DC subset imprinting occurred at the mRNA level from the CDP stage, revealing that subset fate is defined in the BM and not in peripheral tissues. Single cell transcriptome analysis allowed identification of the molecular checkpoints between progenitor stages and revealed new regulators of DC-poiesis, shedding light on the role of cell cycle control and specific transcription factors in DC lineage development. These data advance our knowledge of the steady-state regulation of DC populations and open promising new avenues for investigation of the therapeutic potential of DC subset-specific targeting in vivo to improve vaccine-based and immunotherapeutic strategies.
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