Multiome-based identification of HSC subtype markers shows that ageing, but not inflammatory stress, increases HSC platelet bias

Single-cell transplantation assays have revealed that the HSC compartment contains lineage-restricted subtypes capable of reconstituting only specific lineages, such as platelets, alongside true multi-lineage HSCs. The proportion of these lineage-restricted HSCs increases with age, contributing to declined immunity and potentially to clonal haematopoiesis.

To date, their identification and isolation have primarily relied on transgenic reporters, such as the Vwf-EGFP mouse line, which offer only moderate accuracy. In this study, we profiled highly purified adult mouse long-term HSCs (LT-HSCs; LSK CD48⁻ CD150⁺ CD34⁻) using the DOGMAseq platform, which enables simultaneous measurement of transcriptome (RNA-seq), chromatin accessibility (ATAC-seq), and surface protein expression (CITE-seq).