The spatiotemporal expression patterns of MSC-associated markers contribute to the identification of progenitor subpopulations in developing limbs

During limb development, skeletal tissues differentiate from their progenitor cells in an orchestrated manner. Mesenchymal stromal cells (MSCs), which are considered to be adult undifferentiated/progenitor cells, have traditionally been identified by the expression of MSC-associated markers (MSC-am) and their differentiation capacities. However, although MSCs have been isolated from bone marrow and a variety of adult tissues, their developmental origin is poorly understood. Remarkably, adult MSCs share similar differentiation characteristics with limb progenitors. Here, we determined the expression patterns of common MSC-am throughout mouse hindlimb development. Our results demonstrate that MSC-am expression is not restricted to undifferentiated cells in vivo. Results from the analysis of MSC-am spatiotemporal expression in the embryonic hindlimb allowed us to propose five subpopulations which represent all limb tissues that potentially correspond to progenitor cells for each lineage. This work contributes to the understanding of MSC-am expression dynamics throughout development and underlines the importance of considering their expression patterns in future MSC studies of the limb.