Multi-dimensional characterization of a human cDC2 homeostatic maturation program by single-cell multi-omics

To gain insights into the homeostatic maturation program of human cDCs at multiple dimensions, we exploited the nature of the spleen where DC maturation leads to migration from the red pulp and marginal zone to the white pulp of the spleen. Therefore, all steps of DC maturation are present and can be studied in the same organ. We utilized the Chromium Single Cell Multiome ATAC + Gene Expression technique to depict the chromatin accessibility and nucleic mRNA profiles of lineage- (lin-) CD11c+ HLA-DR+ cells from the spleen of a healthy human donor and characterized a homeostatic maturation of the cDC2 subtype with 3 stages (cDC2, DC2pre-hm, DC2hm) at both transcription and epigenetic levels. Overall design: Single-cell multi-omics (scATAC-seq+snRNA-seq) of lineage- (lin-) CD11c+ HLA-DR+ cells from the spleen of a healthy donor were obtained by MACS and FACS. 10 × Chromium Next GEM Single Cell Multiome ATAC + Gene Expression libraries were prepared according to the manufacturer's instructions. Sequencing was performed using Illumina NovaSeq 6000.