Insights into skeletal stem cells

The tissue-resident skeletal stem cells (SSCs), which are self-renewal and multipotent, continuously provide cells (including chondrocytes, bone cells, marrow adipocytes, and stromal cells) for the development and homeostasis of the skeletal system. In recent decade, utilizing fluorescence-activated cell sorting, lineage tracing, and single-cell sequencing, studies have identified various types of SSCs, plotted the lineage commitment trajectory, and partially revealed their properties under physiological and pathological conditions. In this review, we retrospect to SSCs identification and functional studies. We discuss the principles and approaches to identify bona fide SSCs, highlighting pioneering findings that plot the lineage atlas of SSCs. The roles of SSCs and progenitors in long bone, craniofacial tissues, and periosteum are systematically discussed. We further focus on disputes and challenges in SSC research.