Aged Stem Cells with High Mitochondrial Mass Still Renew and GPR183 Marks Them

A new Nature Aging study reports that only a fraction of aged HSCs preserves long-term regenerative capacity, and they can be identified by high mitochondrial mass. These mito-Dendra2^High HSCs generated more donor-derived long-term HSCs 16 weeks after transplantation than their mito-Dendra2^Low counterparts, despite producing similar peripheral blood output.

Single-cell transcriptomics showed that this subset maintains elevated autophagy, mitophagy, iron handling, and mitochondrial quality-control pathways. A surface marker, GPR183, was tightly correlated with the mito-High state. Using Anti-GPR183 (extracellular)-FITC Antibody (#AGR-063-F) and flow cytometry, researchers isolated GPR183^High aged HSCs – the population that retained self-renewal, stem identity in culture, and reduced differentiation bias.

These novel results define a functionally resilient HSC pool and provide a practical marker to isolate it.

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