Deciphering postnatal limb development at single-cell resolution.

The early postnatal limb developmental progression bridges embryonic and mature stages and mirrors the pathological remodeling of articular cartilage. However, compared with multitudinous research on embryonic limb development, the early postnatal stage seems relatively unnoticed. Here, a systematic work to portray the postnatal limb developmental landscape was carried out by characterization of 19,952 single cells from murine hindlimbs at 4 postnatal stages using single-cell RNA sequencing technique. By delineation of cell heterogeneity, the candidate progenitor sub-clusters marked by Cd34 and Ly6e were discovered in articular cartilage and enthesis, and three cellular developmental branches marked by Col10a1, Spp1, and Tnni2 were reflected in growth plate. The representative transcriptomes and developmental patterns were intensively explored, and the key regulation mechanisms as well as evolvement in osteoarthritis were discussed. Above all, these results expand horizons of postnatal limb developmental biology and reach the interconnections between limb development, remodeling, and regeneration.