A Dynamic Stem Cell State Links Environmental Cues to Skeletal and Regenerative Fates

Panx3 marks a dynamic functional state within bona fide skeletal stem cells, enabling long-term clonal persistence and multipotency while being inducible by development, stimulation, and injury.

• Why it matters: It remains unclear how aging and injury–linked environmental cues reshape skeletal stem cell identity and regenerative output across maturing anatomical niches.
• What they did: Using spatially informed single-cell transcriptomics, the study identified Panx3 in rare SSCs and created Panx3-CreERT2 mice to track the state longitudinally.
• The result: Panx3+ SSCs persist and self-renew, osteoanabolic stimulation expands existing Panx3 clones, and injury induces Panx3 locally in unlabeled progenitors, with niche signals redirecting Panx3-lineage cells toward durable cartilage regeneration in aged and osteoarthritic joints and with human SSCs.

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