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

Abstract

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 like the sclerotome cells in the embryonic stage, osteo-chondroprogenitors in growing long bones, and skeletal stem cells of bone marrow in the postnatal period. However, the exact origins of progenitor cells, their lineage relationships, and their potential to differentiate into osteoblasts and chondroblasts from embryos to adult tissues are not well understood. In this study, we conducted clonal cell tracking in zebrafish and showed that sox9a⁺ cells are already 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 animal life, even through regeneration. In addition, we further revealed that only osteogenic mesenchymal cells replenish the osteoblast progenitor cells (OPCs), a population of reserved tissue stem cells found to be involved in the de novo production of osteoblasts during regeneration and homeostasis in zebrafish. Thus, our clonal cell tracking study in zebrafish firstly revealed that the mesenchymal progenitor cells that are fated to develop into either chondroblasts or osteoblasts serve as respective tissue stem cells to maintain skeletal tissue homeostasis. Such mesenchymal progenitors dedicated to producing either chondroblasts or osteoblasts would be important targets for skeletal tissue regeneration.