Independent mesenchymal progenitor pools respectively produce and maintain osteogenic and chondrogenic cells in zebrafish

Skeletal tissues including cartilage and bones are characteristic features of vertebrates that are crucial for supporting body morphology and locomotion. Studies mainly in mice have shown that osteoblasts and chondroblasts are supplied from several progenitors in development, growth, and homeostasis. However, developmental origins of osteoblasts and chondroblasts, lineage relationship, progenitor cells, and their differentiation potentials throughout animal life are not seamlessly understood. In this study, we used clonal cell tracking in zebrafish and found that sox9a+ cells are committed to either chondrogenic or osteogenic fates during embryonic stages, and that respective progenies are independently maintained as mesenchymal progenitor pools. Once committed, they never change their lineage identities throughout their lives, even through regeneration. We further showed that osteogenic mesenchymal cells replenish the osteoblast progenitor cells, OPCs, which are the reserved stem cells for osteoblast production during regeneration and homeostasis. Independent mesenchymal progenitors dedicated to produce either chondroblasts or osteoblasts would be important targets for skeletal tissue regeneration. To investigate the lineage relationship between mesenchymal cells and osteoblasts in the zebrafish caudal fin, we isolated sp7- mesenchymal cells and sp7+ osteoblasts derived from sox9a+ somite cells from 14 days post amputation (dpa) caudal fin by fluorescence-activated cell sorting. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cells. Comparative gene expression profiling analysis of RNA seq data for osteogenic mesenchymal progenitors (OMPs), chondrogenic mesenchymal progenitors (CMPs), and osteoblasts.