Lgr5 and Col22a1 mark progenitor cells in the lineage toward juvenile articular chondrocytes

The synovial joint forms from a pool of progenitor cells in the interzone region of the future joint. Expression of Gdf5 and Wnt9a has been used to mark the earliest cellular processes in the formation of the interzone and the progenitor cells. However, progression and lineage specification toward the different tissues of the joint is not well understood. Here, by lineage tracing studies we identify a population of Lgr5+ interzone cells that contribute to the formation of cruciate ligaments, synovial membrane and articular chondrocytes of the joint. This is supported by single cell transcriptome analyses. Furthermore, we showed that Col22a1, a marker of early articular chondrocytes, co-expresses with Lgr5+ cells prior to cavitation as an important lineage marker specifying the progression towards articular chondrocytes. Lgr5+ cells contribute to the repair of a joint defect with the re-establishment of Col22a1 containing superficial layer. Knee joint and surrounding tissue was obtained from E14.5 Lgr5GPF/+ (https://www.jax.org/strain/008875) embryos and digested with enzyme for 10x genomics single cell analysis