A single-cell transcriptomic atlas characterizes age-related changes of murine cranial stem cell niches

The craniofacial bones provide structural support for the skull and accommodate the vulnerable brain tissue with a protective cavity. The bone tissue undergoes constant turnover, which relies on skeletal stem cells (SSCs) and/or mesenchymal stem cells (MSCs) and their niches. SSCs/MSCs and their perivascular niche within the bone marrow are well characterized in long bones. As for cranial bones, besides bone marrow, the suture mesenchyme has been identified as a unique niche for SSCs/MSCs of craniofacial bones. However, a comprehensive study of the two different cranial stem cell niches at single-cell resolution is still lacking. In addition, during the progression of aging, age-associated changes in cranial stem cell niches and resident cells remain uncovered. In this study, we investigated age-related changes in cranial stem cell niches via single-cell RNA sequencing (scRNA-seq). The transcriptomic profiles and cellular compositions have been delineated, indicating alterations of the cranial bone marrow microenvironment influenced by inflammaging. Moreover, we identified a senescent mesenchymal cell subcluster and several age-related immune cell subclusters by reclustering and pseudotime trajectory analysis, which might be closely linked to inflammaging. Finally, differentially expressed genes (DEGs) and cell-cell communications were analyzed during aging, revealing potential regulatory factors. Overall, this work highlights the age-related changes in cranial stem cell niches, which deepens the current understanding of cranial bone and suture biology and may provide therapeutic targets for antiaging and regenerative medicine.