Defining the marker and developmental trajectory of myeloid-derived suppressor cells in aging by single-cell transcriptomics

Myeloid-derived suppressor cells (MDSCs) are recognized as a key mediator of immunosuppression in aging, which induce immunosenescence and increase elderly people's susceptibility to infections, cancers, autoimmune diseases, and degenerative diseases. However, the commonly used MDSC markers overlap with those defining healthy and normal neutrophils or monocytes, which makes it challenging to distinguish MDSCs from their myeloid counterparts, and hampers deeper understanding of the pathophysiological functions of MDSCs. In this study, we compared MDSCs from aged mice to young controls using single-cell RNA sequencing. We established MDSC-specific gene signature, which revealed the general characteristics of MDSCs during aging, and thus facilitating distinguishing them from normal myeloid cells. Experimental study revealed that CD300c may serve as a specific marker for improved detection and enrichment of MDSCs in aging. CD11b⁺Gr1⁺CD300c⁺ cells demonstrated a robust ability of T cell suppression. The universality and applicability of MDSC-specific gene signature have also been demonstrated in human myeloid cells. We also found that MDSCs from aged individuals shared the similar developmental trajectory with their myeloid counterparts, and may develop from mature myeloid cells, both in mice and human beings, which has been reported by a limited number of studies. Overall, our work extends the understanding of MDSCs in aging process.