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Chromatin bindings of IRF4 in the bone marrow-derived conventional dendritic cell 2 (cDC2) cultured with Flt3L

ABSTRACT: We performed ChIP-seq to analyze chromatin bindings of IRF4 transcription factor in cDC2.

ORGANISM(S): Mus musculus

PROVIDER: GSE174011 | GEO | 2021/05/07

REPOSITORIES: GEO

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Chromatin bindings of IRF4 in the bone marrow-derived conventional dendritic cell 2 (cDC2) cultured with Flt3L

Project description:Chromatin bindings of IRF4 in the bone marrow-derived conventional dendritic cell 2 (cDC2) cultured with Flt3L

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Project description:Conventional Dendritic Cells (cDC) are antigen-presenting cells comprising cDC1 and cDC2 subsets, responsible for priming naïve CD8+ and CD4+ T cells, respectively. Recent studies have unveiled cDC2 heterogeneity and identified various cDC2 progenitors beyond the common DC progenitor (CDP), hinting at distinct cDC2 lineages. By generating Cd300ciCre-hCD2R26tdTomato reporter mice, we identified a bone marrow pro-cDC2 progenitor exclusively generating cDC2 in vitro and in vivo. Single-cell analyses and multiparametric flow cytometry demonstrated that pro-cDC2 encompass myeloid-derived pre-cDC2 and lymphoid-derived pDC-like precursors differentiating into a transcriptionally convergent cDC2 phenotype. Cd300c-traced cDC2 had distinct transcriptomic profiles, phenotypes, and tissue distributions compared to Ms4a3CreR26tdTomato lineage-traced DC3, a monocyte-DC progenitor-derived subset that bypasses CDP. Mice with reduced Cd300c-traced cDC2 showed impaired humoral responses to a blood-borne antigen. We conclude that progenitors of distinct lineages shape the diversity of mature cDC2 cells across tissues. Thus, ontogenesis may impact tissue immune responses.

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