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

Abstract 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.