Gli1 labels progenitors during chondrogenesis in postnatal mice

Skeletal growth promoted by endochondral ossification is tightly coordinated by self-renewal and differentiation of chondrogenic progenitors. Emerging evidence has shown that multiple skeletal stem cells (SSCs) participate in cartilage formation. However, as yet, no study has reported the existence of common long-lasting chondrogenic progenitors in various types of cartilage. Here, we identify Gli1⁺ chondrogenic progenitors (Gli1⁺ CPs), which are distinct from PTHrP⁺ or FoxA2⁺ SSCs, are responsible for the lifelong generation of chondrocytes in the growth plate, vertebrae, ribs, and other cartilage. The absence of Gli1⁺ CPs leads to cartilage defects and dwarfishness phenotype in mice. Furthermore, we show that the BMP signal plays an important role in self-renewal and maintenance of Gli1⁺ CPs. Deletion of Bmpr1α triggers Gli1⁺ CPs quiescence exit and causes the exhaustion of Gli1⁺ CPs, consequently disrupting columnar cartilage. Collectively, our data demonstrate that Gli1⁺ CPs are common long-term chondrogenic progenitors in multiple types of cartilage and are essential to maintain cartilage homeostasis.